Amino-1,3,5-triazines N-substituted with chiral bicyclic radicals, process for their preparation, compositions thereof, and their use as herbicides and plant growth regulators

ABSTRACT

The invention related to an optically active compound of formula (I) or a salt thereof: 
     
       
         
         
             
             
         
       
     
     wherein the various symbols are as defined in the description, to processes for their preparation, to compositions thereof, and to their use as herbicides or plant growth regulators. The invention also relates to novel intermediates of formula (III), (V) and (XIII) as defined in the description.

Amino-1,3,5-triazines N-substituted with chiral bicyclic radicals,process for their preparation, compositions thereof, and their use asherbicides and plant growth regulators.

The invention relates to optically active isomers of some2-amino-4-(bicyclyl)amino-6-(substituted alkyl)-1,3,5-triazinederivatives, processes for their preparation, to compositions andintermediates thereof, and to their use as herbicides or plant growthregulators for the control of undesired plants or vegetation.

BACKGROUND OF THE INVENTION

WO 97/31904 and EP-A-0864567 describe the preparation of2-amino-4-bicyclyl-amino-1,3,5-triazines and their use as herbicides andplant growth regulators. The reference generically describes variousamino-1,3,5-triazine derivatives which are substituted with someradicals comprising one or more centres of chirality in principle. Thespecifically disclosed derivatives, however, were described as mixturesof stereoisomers only, such as racemic mixtures of enantiomers ormixtures of diastereomers in their racemic forms. In some cases, theknown active substances have disadvantages when used, for example havean insufficient herbicidal action against harmful plants, too rigidapplicational limitations related to weather, climate and/or soilconditions, too narrow a spectrum against weeds or too little cropselectivity.

It has now been found that surprisingly specific optically activeisomers of certain substituted 2-amino-1,3,5-triazine derivativespossess advantageous applicational properties compared with the priorart compounds or corresponding racemic compounds or other opticalisomers thereof.

For instance they are very active herbicides which can be used for thecontrol of a range of harmful weeds, having surprisingly more potentherbicidal efficacy than stereoisomers thereof or racemic mixturesthereof.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a compound which is an optically activecompound of formula (I):

in which:R¹ is H, halogen, (C₁-C₆)alkyl, (C₁-C₆)haloalkyl,[(C₁-C₄)alkoxy](C₁-C₆)alkyl, (C₃-C₆)cycloalkyl which is unsubstituted orsubstituted by one or more radicals selected from the group of halogen,(C₁-C₄)alkyl and (C₁-C₄)haloalkyl, or is (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₂-C₆)haloalkenyl, (C₄-C₆)cycloalkenyl, (C₄-C₆)halocycloalkenyl,(C₁-C₆)alkoxy or (C₁-C₆)haloalkoxy;R² is H, halogen, (C₁-C₆)alkyl or (C₁-C₄)alkoxy; orR¹ and R² can together with the attached carbon atom form a(C₃-C₆)cycloalkyl or (C₄-C₆)cycloalkenyl ring;R³ is H, (C₁-C₆)alkyl, (C₁-C₄)alkoxy or halogen;R⁴ and R⁵ are each independently H, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl,(C₃-C₄)alkenyl, (C₃-C₄)haloalkenyl, (C₃-C₄)alkynyl, (C₃-C₄)haloalkynylor an acyl radical;R⁶ is H, (C₁-C₆)alkyl or (C₁-C₆)alkoxy;R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₄)alkyl,(C₁-C₃)haloalkyl, halogen, (C₁-C₃)alkoxy, (C₁-C₃)haloalkoxy or CN;A is CH₂, O or a direct bond;and the stereochemical configuration at the marked 1 position is (R)having a stereochemical purity of from 60 to 100% (R), preferably70-100% (R), in particular 80-100% (R), based on the content ofstereoisomers having (R)- and (S)-configurations at this position;or an agriculturally acceptable salt thereof.

For reference purposes in formula (I) certain ring carbon atoms aremarked from 1 to 3, whilst the carbon atom bonded to the triazine ringis marked 1*.

In the present invention the stereochemical configuration at the marked1 position is fixed as being predominantly (R) according to theCahn-Ingold-Prelog system, however the subject matter of the inventionis also directed to all stereoisomers at other locants which areencompassed by formula (I), and their mixtures. Such compounds of theformula (I) contain, e.g. one or more additional asymmetric carbon atomsor else double bonds which are not stated specifically in the formula(I). It will be understood that the present invention embraces both thepure isomers and more or less enriched mixtures thereof, where theasymmetric carbon atom in marked 1 position is in the R-configurationor, in mixtures, a compound or compounds of same chemical constitutionhave the R-configuration in marked 1 position or are present in a ratiothat compounds having the R-configuration are predominantly present (atleast 60% R-configuration) whilst the other asymmetric carbon atom(s)may be present in racemic form or are more or less resolved too.Provided the condition for the stereochemical configuration at marked 1position is met, the possible stereoisomers which are defined by theirspecific spatial form, such as enantiomers, diastereomers, Z- andE-isomers, are all encompassed by formula (I) and can be obtained bycustomary methods from mixtures of the stereoisomers, or else beprepared by stereoselective reactions in combination with the use ofstereochemically pure starting materials.

Dependent on the definition of the radicals R¹, R² and R³ one possibleadditional centre of asymmetry referred to above is the carbon atommarked 1* in formula (I), in which case the compound of formula (I)according to the invention can exist as at least two pure stereoisomericforms, i.e. (1R,1*R) and (1R,1*S) selected from the four purestereoisomers which exist in principle. A further centre of asymmetrymay also be present at the carbon atom marked 2 in formula (I), in whichcase the compound of the invention can exist as at least four purestereoisomeric forms, each of these additional asymmetric carbon atomshaving (R) or (S) configuration according to the Cahn-Ingold-Prelogsystem, i.e. pure isomers having the configuration (1R,1*R,2R),(1R,1*R,2S), (1R,1*S,2R) and (1R,1*S,2S), selected from the eight purestereoisomers which exist in principle. Moreover depending on the natureof the groups R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰, furtherasymmetric carbon atoms may be present.

Where in the formulae shown hereinafter, a specific stereochemicalconfiguration is defined at any position, for example at the carbon atommarked 1, 2 or 1*, unless otherwise defined, it means that thestereochemical purity at the marked position is 60 to 100%, preferably70-100%, in particular 80-100%, most preferably 100%.

“Stereochemical purity” means the amount of the stated stereoisomerexpressed as a percentage of the total amount of stereoisomers havingthe given chiral centre.

The invention also encompasses any keto and enol tautomer forms andmixtures and salts thereof, if respective functional groups are present.

The compounds of the formula (I) can form salts by addition of asuitable inorganic or organic acid such as, for example, HCl, HBr, H₂SO₄or HNO₃, or a mono- or bifunctional carboxylic acid or sulfonic acid, toa basic group such as, for example, amino or alkylamino.

Some compounds of the formula (I) can form salts by addition of asuitable inorganic or organic base. Such compounds (I) have a functionalgroup which contain an “acidic hydrogen atom”, such as the carboxyl orthe sulfonyl group, which may be a substituent in the definition of theacyl group. Examples of these salts are metal salts, particularlyalkaline metal salts or alkaline earth metal salts, preferably, sodium-or potassium salts, or unsubstituted or substituted ammonium salts, suchas ammonium salts or salts of organic amines, or quaternary ammoniumsalts.

In the present patent specification, including the accompanying claims,the aforementioned substituents have the following meanings:

Halogen means fluorine, chlorine, bromine or iodine.

The term “halo” before the name of a radical means that this radical ispartially or completely halogenated, that is to say, substituted by F,Cl, Br, or I, in any combination.

The expression “(C₁-C₆)alkyl” means an unbranched or branched non-cyclicsaturated hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms(indicated by a range of C-atoms in the parenthesis), such as, forexample a methyl, ethyl, propyl, isopropyl, 1-butyl, 2-butyl,2-methylpropyl or tert-butyl radical. The same applies to alkyl groupsin composite radicals such as “alkoxyalkyl”.

Alkyl radicals and also in composite groups, unless otherwise defined,preferably have 1 to 4 carbon atoms.

“(C₁-C₆)Haloalkyl” means an alkyl group mentioned under the expression“(C₁-C₆)alkyl” in which one or more hydrogen atoms are replaced by thesame number of identical or different halogen atoms, such asmonohaloalkyl, e.g. CH₂F, CH₂Cl, CH₂Br, CH₂I, CH₂CH₂F, CH₂CH₂Cl,CH₂CH₂Br, CH₂CH₂I, CHFCH₃, or perhaloalkyl, such as CF₃, CCl₃, CF₂CF₃,CCl₂CCl₃, CF₂CCl₃ and CCl₂CClF₂, or CHF₂, CF₃CH₂, CHF₂CF₂, CH₂FCHCl orCHCl₂. “(C₁-C₄)Haloalkyl” is preferred, particularly monohaloalkyl,perhaloalkyl, CF₃, CHF₂, CH₂F, CHFCH₃,CF₂CF₃, CH₂FCHCl, CH₂Cl, CCl₃,CHCl₂ or CH₂CH₂Cl;

“[(C₁-C₄)Alkoxy](C₁-C₆)alkyl” means (C₁-C₆)alkyl which is substituted by(C₁-C₄)alkoxy.

“(C₁-C₆)Alkoxy” means an alkoxy group whose carbon chain has the meaninggiven under the expression “(C₁-C₆)alkyl”. “Haloalkoxy” is, for example,OCF₃, OCHF₂, OCH₂F, CF₃CF₂O, OCH₂CF₃ or OCH₂CH₂Cl.

“(C₂-C₆)Alkenyl” means an, unbranched or branched non-cyclic carbonchain having a number of carbon atoms which corresponds to this statedrange and which contains at least one double bond which can be locatedin any position of the respective unsaturated radical. “(C₂-C₆)Alkenyl”accordingly denotes, for example, the vinyl, allyl, 2-methyl-2-propenyl,2-butenyl, pentenyl, 2-methylpentenyl or the hexenyl group.

“(C₂-C₆)Alkynyl” means an unbranched or branched non-cyclic carbon chainhaving a number of carbon atoms which corresponds to this stated rangeand which contains one triple bond which can be located in any positionof the respective unsaturated radical.

“(C₂-C₆)Alkynyl” accordingly denotes, for example, the propargyl,1-methyl-2-propynyl, 2-butynyl or 3-butynyl group.

“(C₃-C₆)Cycloalkyl” denotes monocyclic alkyl radicals, such as thecyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical.

“(C₄-C₆)Cycloalkenyl” denotes a carbocyclic, nonaromatic, partiallyunsaturated ring having 4 to 6 carbon atoms, for example 1-cyclobutenyl,2-cyclobutenyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, or1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 1,3-cyclohexadienyl or1,4-cyclohexadienyl.

An acyl radical is, in a broad sense, the radical of an organic acidwhich is formed formally by removing an OH group, for example theradical of a carboxylic acid and radicals of acids derived therefrom,such as thiocarboxylic acid, unsubstituted or N-substitutediminocarboxylic acids or the radical of carbonic monoesters,unsubstituted or N-substituted carbamic acid, unsubstituted orN-substituted thiocarbamic acid, sulfonic acids, sulfinic acids,phosphonic acids, and phosphinic acids. Acyl is, for example, formyl,alkylcarbonyl such as [(C₁-C₄)alkyl]carbonyl, phenylcarbonyl,alkyloxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, alkylsulfonyl,alkylsulfinyl, phenylsulfonyl, N-alkyl-1-iminoalkyl and other radicalsof organic acids. In this context, the radicals can be even furthersubstituted in each of the alkyl or phenyl moieties, for example in thealkyl moiety by one or more'radicals selected from the group consistingof halogen, alkoxy, phenyl and phenoxy; examples of substituents in thephenyl moiety are mono- or polysubstituted, preferably up totrisubstituted, identical or different radicals selected from the groupconsisting of halogen, (C₁-C₄)alkyl, (C₁-C₄)alkoxy, (C₁-C₄)haloalkyl,(C₁-C₄)haloalkoxy, and nitro, for example o-, m- and p-tolyl,dimethylphenyls, 2-, 3- and 4-chlorophenyl, 2-, 3- and 4-trifluoro- and-trichlorophenyl, 2,4-, 3,5-, 2,5- and 2,3-dichlorophenyl, o-, m- andp-methoxyphenyl.

The acyl radical usually has 1 to 24 carbon atoms, preferably 1 to 18,more preferably 1 to 12, most preferably 1 to 7, in particular 1 to 4.

Acyl in the narrower sense is, for example, the radical of an alkanoicacid, alkenoic acid, alkynoic acid or arylcarboxylic acid (for examplebenzoyl), or is for example alkoxycarbonyl, alkenyloxycarbonyl,alkynyloxycarbonyl, aryloxycarbonyl, alkylsulfonyl, alkysulfinyl orphenylsulfonyl; in an even narrower sense, acyl is a radical of analkanoic acid, for example a (C₁-C₂₄)alkanoic acid, preferably(C₁-C₁₈)alkanoic acid, in particular (C₁-C₁₂)alkanoic acid, veryespecially (C₁-C₆)alkanoic acid such as formyl, acetyl or propionyl.

The expression “one or more radicals selected from the group consistingof” in the definition is to be understood as meaning in each case one ormore identical or different radicals selected from the stated group ofradicals, unless specific limitations are defined expressly.

By combination of variables the generic formulae may formally defineunstable functional groups, e.g. the carbamyl radical or the hydroxycarbonyloxy radical, which are unstable in neutral or acidic aqueousmedium and which thus are not preferred or are used by way of theirstable salts or degradation products only, respectively.

Compounds of the stated formula (I) according to the invention or theirsalts in which individual radicals have one of the preferred meaningswhich have already been stated or are stated hereinbelow, andparticularly those shown: in the Table examples, or in particular thosein which two or more of the preferred meanings which have already beenstated or which are stated hereinbelow are combined, are of particularinterest, mainly because of the more potent herbicidal action, betterselectivity and/or greater ease of preparation.

Of particular interest are compounds of formula (I) where a radicalselected from the group of radicals R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹,R¹⁰ and A is preferably defined as set forth below, wherein thedefinition of the radical is independent from the definitions of theother radicals of said group. Preferred compounds of formula (I) containa combination of radicals of said group which comprise two or morepreferred meanings set forth below.

In the following preferred definitions it is generally to be understoodthat where symbols are not specifically defined they are to be aspreviously defined in the description.

Preferably R¹ is H, halogen, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl,[(C₁-C₄)alkoxy](C₁-C₄)alkyl, (C₃-C₆)cycloalkyl which is unsubstituted orsubstituted by one or more, preferably one or two (C₁-C₄)alkyl groups,or is (C₃-C₄)halocycloalkyl, (C₂-C₄)alkenyl, (C₂-C₄)alkynyl,(C₂-C₄)haloalkenyl, (C₁-C₄)alkoxy or (C₁-C₄)haloalkoxy; more preferablyR¹ is H, halogen, (C₁-C₄)alkyl, (C₃-C₆)cycloalkyl or (C₁-C₄)alkoxy; yetmore preferably R¹ is, H or (C₁-C₄)alkyl; most preferably R¹ is H or(C₁-C₃)alkyl, in particular H, methyl or ethyl.

Preferably R² is H or (C₁-C₄)alkyl; more preferably R² is H.

Preferably R¹ and R² together with the attached carbon atom form a(C₃-C₆)cycloalkyl ring, in particular (C₃-C₄)cycloalkyl.

Preferably R³ is H, (C₁-C₄)alkyl, (C₁-C₄)alkoxy or halogen; morepreferably R³ is H, (C₁-C₃)alkyl, (C₁-C₄)alkoxy, Cl or F; yet morepreferably R³ is H, (C₁-C₂)alkyl, methoxy, chloro or fluoro.

Preferably R⁴ is H, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₃-C₄)alkenyl,(C₃-C₄)alkynyl or an acyl radical having 1 to 12 carbon atoms, the acylradical is preferably selected from the group consisting of CHO,—CO(C₁-C₆)alkyl, —CO(C₁-C₆)haloalkyl, —CO₂(C₁-C₆)alkyl,—SO₂(C₁-C₆)alkyl, —CO₂-phenyl or —CO-phenyl wherein each phenyl isunsubstituted or substituted by one or more radicals selected from thegroup consisting of halogen, (C₁-C₂)alkyl, (C₁-C₂)haloalkyl,(C₁-C₂)alkoxy, (C₁-C₂)haloalkoxy and NO₂;

more preferably R⁴ is H, (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, allyl,propargyl, CHO, —CO(C₁-C₃)alkyl or —CO(C₁-C₃)haloalkyl; yet morepreferably R⁴ is H, CHO, COCH₃, COCH₂Cl, COCH(CH₃)Cl or COCF₃; mostpreferably R⁴ is H.

Preferably R⁵ is H, (C₁-C₄)alkyl or (C₁-C₄)haloalkyl; more preferably R⁵is H or (C₁-C₂)alkyl; most preferably R⁵ is H.

Preferably R⁶ is H, (C₁-C₃)alkyl or (C₁-C₃)alkoxy; more preferably R⁶ isH, methyl or ethyl.

Preferably R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₃)alkyl,halogen or (C₁-C₃)alkoxy; more preferably R⁷, R⁸, R⁹ and R¹⁰ are eachindependently H, methyl, F or Cl.

Preferably A is CH₂ or a direct bond.

Preferred compounds of formula (I) are those in which:

R¹ is H, halogen, (C₁-C₄)alkyl, such as methyl, ethyl, n-propyl oriso-propyl, or is (C₁-C₄)haloalkyl, [(C₁-C₄)alkoxy](C₁-C₄)alkyl,(C₃-C₆)cycloalkyl which is unsubstituted or substituted by one or two(C₁-C₄)alkyl groups, or is (C₃-C₄)halocycloalkyl, (C₂-C₄)alkenyl,(C₂-C₄)haloalkenyl, (C₂-C₄)alkynyl, (C₁-C₄)alkoxy or (C₁-C₄)haloalkoxy;R² is H or (C₁-C₄)alkyl; orR¹ and R² together with the attached carbon atom form a(C₃-C₆)cycloalkyl ring;R³ is H, (C₁-C₄)alkyl, (C₁-C₂)alkoxy or halogen (more preferably H,(C₁-C₃)alkyl, methoxy, Cl or F);R⁴ is H, (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₃-C₄)alkenyl, (C₃-C₄)alkynylor an acyl radical having 1 to 12 carbon atoms (preferably CHO,—CO(C₁-C₆)alkyl, —CO(C₁-C₆)haloalkyl, —CO₂(C₁-C₆)alkyl,—SO₂(C₁-C₆)alkyl, —CO₂-phenyl or —CO-phenyl wherein each phenyl isunsubstituted or substituted by one or more radicals selected from thegroup consisting of halogen, (C₁-C₂)alkyl, (C₁-C₂)haloalkyl,(C₁-C₂)alkoxy, (C₁-C₂)haloalkoxy and NO₂);R⁵ is H, (C₁-C₄)alkyl or (C₁-C₄)haloalkyl;R⁶ is H, (C₁-C₃)alkyl or (C₁-C₃)alkoxy;R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₃)alkyl, halogen or(C₁-C₃)alkoxy; andA is CH₂, O or a direct bond (preferably A is CH₂ or a direct bond, inparticular a direct bond).

More preferred compounds of formula (I) are those in which:

R¹ is H or (C₁-C₃)alkyl;R² is H or (C₁-C₃)alkyl; orR¹ and R² together with the attached carbon atom form a(C₃-C₄)cycloalkyl ring;R³ is H, (C₁-C₂)alkyl, methoxy, Cl or F;R⁴ is H, (C₁-C₃)alkyl, (C₁-C₃)haloalkyl, allyl, propargyl, CHO,—CO(C₁-C₃)alkyl or —CO(C₁-C₃)haloalkyl;R⁵ is H or (C₁-C₂)alkyl;R⁶ is H, (C₁-C₃)alkyl or (C₁-C₃)alkoxy;R⁷, R⁸, R⁹ and R¹⁰ are each independently H, methyl, F and Cl; andA is CH₂, O or a direct bond (preferably A is CH₂ or a direct bond, inparticular a direct bond).

Especially preferred compounds of formula (I) are those in which:

R¹ is H or (C₁-C₂)alkyl;R² is H or (C₁-C₂)alkyl; orR¹ and R² together with the attached carbon atom form a cyclopropylring;R³ is H, (C₁-C₂)alkyl, Cl or F;

R⁴ is H; R⁵ is H;

R⁶ is H or (C₁-C₃)alkyl;R⁷, R⁸, R⁹ and R¹⁰ are each independently selected from the groupconsisting of H, methyl, F and Cl; andA is CH₂, O or a direct bond.

Preferably the radical of the formula CR¹R²R³ in formula (I) is aradical selected from the group consisting of (C₁-C₄)alkyl,(C₁-C₄)haloalkyl, (C₃-C₄)cycloalkyl, 1-(C₁-C₃)alkyl-(C₃-C₄)-cycloalkyland (C₃-C₄)halocycloalkyl, more preferably (C₁-C₃)alkyl,(C₁-C₄)fluoroalkyl, (C₁-C₄)chloroalkyl, (C₃-C₄)cycloalkyl,1-(C₁-C₃)alkyl-(C₃-C₄)-cycloalkyl, (C₃-C₄)-fluorocycloalkyl or(C₃-C₄)chlorocycloalkyl, for example radicals such as methyl, ethyl,n-propyl, i-propyl, n-butyl, 2-butyl, i-butyl, tert-butyl,1-fluoro-ethyl, 1-fluoro-propyl, 1-fluoro-isopropyl, 1-fluoro-n-butyl,1-chloro-ethyl, 1-chloro-propyl, 1-chloro-isopropyl, 1-chloro-n-butyl,1-methyl-cyclopropyl, 1-chloro-cyclopropyl or 1-fluoro-cyclopropyl.

A preferred embodiment of the invention relates to optically activecompounds of formula (Ia) in which the carbon atoms marked 1 and 1* areboth chiral and the carbon atom marked 2 is achiral:

wherein:R¹, R² and R³ are as defined in formula (I) provided that R¹, R² and R³are structurally different;the various other symbols are as defined in formula (I),and the stereochemical configuration at the marked 1 carbon atom is asdefined in formula (I),and the stereochemistry at the marked 1* carbon atom is (R) or (S)configuration or a mixture thereof, also including the racemic mixture(R,S), preferably the racemic configuration or an excess of the (R) or(S) configuration from 60 to 100%, especially from 70 to 100%, mostpreferably from 80 to 100%, based on the total amount of (R) and (S)configuration;or a salt thereof.

More preferred are compounds of formula (Ia) wherein:

R¹ is H, (C₁-C₆)alkyl or (C₁-C₆)alkoxy;R² is H or (C₁-C₄)alkyl;R³ is H, (C₁-C₄)alkyl or halogen;R⁴ and R⁵ are each H;

R⁶ is H;

R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₆)alkyl or halogen;andA is CH₂, O or a direct bond (more preferably A is CH₂ or a direct bond,in particular a direct bond); provided that R¹, R² and R³ arestructurally different.

Yet more preferred are compounds of formula (Ia) wherein:

R¹ is H, methyl or ethyl;

R² is H;

R³ is H, F, Cl, methyl or ethyl;R⁴ and R⁵ are each H;

R⁶ is H;

R⁷, R⁸, R⁹ and R¹⁰ are each independently selected from the groupconsisting of H, methyl, Br, Cl or F; andA is CH₂, O or a direct bond (more preferably A is CH₂ or a direct bond,in particular a direct bond); provided that R¹, R² and R³ arestructurally different.

A second preferred embodiment of the invention relates to opticallyactive compounds of formula (Ib) in which the carbon atoms marked 1 and2 are both chiral and the carbon atom marked 1* is achiral:

wherein:R¹, R² and R³ are as defined in formula (I) provided that at least twoof R¹, R² and R³ are structurally identical;R⁶ is (C₁-C₆)alkyl;the various other symbols are as defined in formula (I);and the stereochemical configuration at the marked 1 carbon atom is asdefined for formula (I);and the stereochemistry at the marked 2 carbon atom is (R) or (S)configuration or a mixture thereof, also including the racemicconfiguration (R,S), preferably the racemic configuration or an excessof the (R) or (S) configuration from 60 to 100%, especially from 70 to100%, most preferably from 80 to 100%, based on the total amount of (R)and (S) configuration;or a salt thereof.

Also preferred are compounds of formula (Ib) wherein:

R¹ is H, (C₁-C₆)alkyl or (C₁-C₆)alkoxy;R² is H or (C₁-C₄)alkyl; orR¹ and R² can together with the attached carbon atom form a(C₃-C₆)cycloalkyl ring;R³ is H, (C₁-C₄)alkyl or halogen;R⁴ and R⁵ are each H;R⁶ is (C₁-C₆)alkyl;R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₆)alkyl or halogen;andA is CH₂, O or a direct bond (more preferably A is CH₂ or a direct bond,in particular a direct bond); provided that at least two of R¹, R² andR³ are structurally identical.

Yet more preferred are compounds of formula (Ib) wherein:

R¹ is H, methyl or ethyl;

R² is H;

R³ is H, F, Cl, methyl or ethyl;R⁴ and R⁵ are each H;R⁶ is (C₁-C₄)alkyl;R⁷, R⁸, R⁹ and R¹⁰ are each independently selected from the groupconsisting of H, methyl, Br, Cl or F; andA is CH₂, O or a direct bond (more preferably A is CH₂ or a direct,bond, in particular a direct bond); provided that at least two of R¹, R²and R³ are structurally identical.

A third preferred embodiment of the invention relates to opticallyactive compounds of formula (Ic) in which the carbon atoms marked 1, 2and 1* are all chiral:

wherein:R¹, R² and R³ areas defined, in formula (I) provided that R¹, R² and R³are structurally different;R⁶ is (C₁-C₆)alkyl, preferably (C₁-C₄)alkyl;the various other symbols are as defined in formula (I);and the stereochemical configuration at the marked 1 carbon atom is asdefined for formula (I);and the stereochemistry at each of the marked 2 and 1* carbon atoms is(R) or (S) configuration or a mixture thereof, also including theracemic configuration (R,S), preferably the racemic configuration or anexcess of the (R) or (S) configuration from 60 to 100%, especially from70 to 100%, most preferably from 80 to 100%, based on the total amountof (R) and (S) configuration;or a salt thereof.

A fourth preferred embodiment of the invention relates to opticallyactive compounds of formula (I) in which the carbon atom marked 1 ischiral, and the carbon atoms marked 2 and 1* are both achiral:

wherein:R¹, R² and R³ are as defined in formula (I) provided that at least twoof R¹, R² and R³ are structurally identical;

R⁶ is H;

the various other symbols are as defined in formula (I);and the stereochemical configuration at the marked 1 position is asdefined for formula (I);or a salt thereof.

Also preferred are compounds of general formula (Id) and (1e) which arestereoisomers of the compounds of general formula (Ia) wherein theconfiguration at the carbon atom marked 1*is specifically defined (R) or(S):

wherein:R¹ is (C₁-C₆)alkyl, (C₁-C₆)haloalkyl or (C₃-C₆)cycloalkyl, preferably(C₁-C₄)alkyl, (C₁-C₄)haloalkyl or (C₃-C₆)cycloalkyl;

R² is H;

R³ is halogen; andthe various other symbols are as defined in formula (I).

Preferred are also compounds of formulae (If), (Ig), (Ih) and (Ii) whichare stereoisomers of the compounds of general formula (Ic) wherein theconfigurations at the carbon atoms marked 1, 2 and 1* are specificallydefined:

and, wherein:R¹ is (C₁-C₆)alkyl, (C₁-C₆)haloalkyl or (C₃-C₆)cycloalkyl;

R² is H;

R³ is (C₁-C₄)alkyl or halogen;R⁶ is (C₁-C₆)alkyl; andthe various other symbols are as defined in formula (I); provided thatR¹, R² and R³ are structurally different.

More preferred are compounds of formula (If), (Ig), (Ih) and (Ii)wherein:

R¹ is methyl or ethyl;

R² is H;

R³ is methyl, ethyl, F or Cl;R⁴ and R⁵ are each H;R⁶ is methyl or ethyl; andR⁷, R⁸, R⁹ and R¹⁰ are each independently H, methyl, Br, Cl or F;provided that R¹, R² and R³ are structurally different.

Also more preferred are compounds of formula (Id) and (Ie) wherein:

R¹ is methyl or ethyl;

R² is H;

R³ is methyl, ethyl, F or Cl;R⁴ and R⁵ are each H; andR⁷, R⁸, R⁹ and R¹⁰ are each independently H, methyl, Br, Cl or F;provided that R¹, R² and R³ are structurally different.

Preferred are also compounds of formula (Ij) which are stereoisomers ofthe compounds of general formula (Ib) wherein the configurations at thecarbon atoms marked 1 and 2 are specifically defined:

wherein:

R¹ is H, (C₁-C₃)alkyl or (C₁-C₃)alkoxy; or

R¹ and R² can together with the attached carbon atom form a(C₃-C₆)cycloalkyl ring;R² is H or (C₇-C₃)alkyl;R³ is H, halogen or (C₁-C₃)alkyl;R⁶ is (C₁-C₆)alkyl; andthe various other symbols are as defined in formula (I);provided that at least two of R¹, R² and R³ are structurally identical.

Also preferred are compounds of formula (Ij) wherein:

R¹ is H, methyl, ethyl, methoxy or Cl;R² is H or methyl; orR¹ and R² can together with the attached carbon atom form a cyclopropylring;R³ is H, methyl, F or Cl;R⁴ and R⁵ are each H;R⁶ is methyl; andR⁷, R⁸, R⁹ and R¹⁰ are each independently selected from the groupconsisting of H, methyl, Br, Cl or F.

Compounds of formula (If) and (Ih) are particularly preferred.

Compounds of formula (If) are most preferred.

A further class of preferred compounds are of formula (Ia), (Ib), (Ic),(Id), (Ie), (If), (Ig), (Ih), (Ii) or (Ij) in which the radicals R¹, R²,R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰ and A are as defined in the preferredmeanings for formula (I).

A particularly preferred class of compounds are those of formula (If)wherein:

R¹ is (C₁-C₂)alkyl;

R² is H;

R³ is (C₁-C₂)alkyl, Cl or F;R⁴ and R⁵ are each H;R⁶ is (C₁-C₂)alkyl;R⁷, R⁸, R⁹ and R¹⁰ are each independently H, methyl, F or Cl; andA is CH₂, O or a direct bond (more preferably A is a direct bond);provided that R¹, R² and R³ are structurally different.

Also preferred are compounds of formula (Ia-1), (Ic-1), (Id-1), (Ie-1),(If-1), (Ig-1), (Ih-1), (Ii-1) and (Ij-1) as depicted as headformulae ofthe tables further below, in which R⁴ and R⁵ are each H, and theradicals R¹, R², R³, R⁶, R⁷, R⁸, R⁹, R¹⁰ and A are as defined above forthe respective basic formulae (Ia), (Ic), (Id), (Ie), (If), (Ig), (Ih),(Ii) and (Ij).

More preferred are compounds of formula (Ia-1), (Id-1) and (Ie-1) asdepicted as headformulae of the tables further below, in which:

R¹ is (C₁-C₆)alkyl;

R² is H;

R³ is (C₁-C₆)alkyl or halogen;R⁴ and R⁵ are each H;

R⁶ is H; and

R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₆)alkyl or halogen;provided that R¹, R² and R³ are structurally different.

Also more preferred are compounds of formula (Ic-1), (If-1), (Ig-1),(Ih-1) and (Ii-1) as depicted as headformulae of the tables furtherbelow, in which:

R¹ is (C₁-C₆)alkyl;

R² is H;

R³ is (C₁-C₆)alkyl or halogen;R⁴ and R⁵ are each H;R⁶ is (C₁-C₆)alkyl; andR⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₆)alkyl or halogen;provided that R¹, R² and R³ are structurally different.

Also more preferred are compounds of formula (Ij-1) as depicted asheadformulae of the tables further below, in which:

R¹ is H, methyl, ethyl, methoxy or Cl;R² is H or methyl; orCR¹R² is cyclopropyl;R³ is H, methyl, Cl or F;R⁴ and R⁵ are each H;R⁶ is methyl; andR⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₆)alkyl or halogen;provided that at least two of R¹, R² and R³ are structurally identical.

Also preferred, are compounds of formula (Ik), (IL), (Im), (In), and(Ip) as depicted as headformulae of the tables further below, in whichthe radicals R¹ to R¹⁰ and A are as defined above in the preferredmeanings of the corresponding general formula.

More preferred are compounds of formula (Ik) as depicted as headformulaeof the tables further below, in which:

R¹ is H, (C₁-C₆)alkyl, halogen or (C₁-C₆)alkoxy;R² is H or (C₁-C₆)alkyl; orCR¹R² is cyclopropyl;R³ is H, (C₁-C₆)alkyl or halogen;R⁴ and R⁵ are each H;

R⁶ is H;

R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₆)alkyl or halogen;and at least two of R¹, R² and R³ are structurally identical.

Also more preferred are compounds of formula (IL), (Im), (In), and (Ip)as depicted as headformulae of the tables further below, in which:

R¹ is (C₁-C₆)alkyl;

R² is H;

R³ is halogen;R⁴ and R⁵ are each H;R⁶ is (C₁-C₆)alkyl;R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₆)alkyl or halogen.

Preferred compounds of formula (I) are optically activeindanylamino-1,3,5-triazine derivatives of formula (I) (A=direct bond).Also preferred are optically active chroman-4-ylamino-1,3,5-triazinederivatives of formula (I) (A=oxygen atom) and optically activetetrahydronaphthalinylamino-1,3,5-triazine derivatives of formula (I)(A=methylene).

Compounds of formula (I) above may be prepared by the application oradaptation of known methods (i.e. methods heretofore used or describedin the literature), for example as generally described in WO 97/31904 orWO 97/29095, and references cited therein, and as hereinafter described.

In the following description where symbols appearing in formulae are notspecifically defined, it is to be understood that they are “ashereinbefore defined” in accordance with the first definition of eachsymbol in the specification, or preferably the preferred definitionsmentioned.

It is to be understood that in the descriptions of the followingprocesses the sequences may be performed in different orders, and thatsuitable protecting groups may be required to achieve the compoundssought.

According to a feature of the present invention compounds of formula (I)may be prepared by the reaction of a compound of general formula (II):

wherein R¹, R² and R³ are as defined in formula (I), and Z is afunctional group selected from the group consisting of carboxylic ester,carboxylic orthoester, carboxylic acid chloride, carboxamide, cyano,carboxylic anhydride or trichloromethyl, with a biguanidine compound offormula (III) or an acid addition salt thereof:

wherein R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰ and A and the configuration at themarked 1 position are as defined in formula (I). The reaction isgenerally performed in the presence of a base, in an inert solvent suchas tetrahydrofuran, dioxan, acetonitrile, N,N-dimethylformamide,methanol or ethanol, at a temperature of from 0° C. to the refluxtemperature of the solvent, preferably at 20° C. to 60° C. The base isgenerally an alkali metal hydroxide, alkali metal hydride, alkali metalcarbonate, alkali metal alkoxide, alkaline earth metal carbonate, or anorganic base such as a tertiary amine for example triethylamine, or1,8-diazabicyclo[5.4.0]undec-7-en (DBU).

According to a further feature of the present invention said compoundsof formula (I) may also be prepared by the reaction of a compound ofgeneral formula (IV):

wherein R¹, R², R³, R⁴ and R⁵ and the configuration at the marked 1*position are as defined in formula (I), and L¹ is a leaving group suchas chlorine, trichloromethyl, (C₁-C₄)-alkylsulfonyl, phenylsulfonyl or(C₁-C₄)alkyl-phenylsulfonyl, with an, amine of formula (V) or an acidaddition salt thereof:

wherein R⁶, R⁷, R⁸, R⁹, R¹⁰ and A and the configuration at the marked 1position are as defined in formula (I). The reaction is generallyperformed in the presence of a base, in an inert solvent e.g. a polarorganic solvent such as tetrahydrofuran, dioxan, acetonitrile,N,N-dimethylformamide, methanol or ethanol, at a temperature of from 0°C. to the reflux temperature of the solvent, preferably at 20° C. to100° C. The base is generally an alkali metal hydroxide, alkali metalhydride, alkali metal carbonate, alkali metal, alkoxide, alkaline earthmetal carbonate, or an organic base such as a tertiary amine for exampletriethylamine, or 1,8-diazabicyclo[5.4.0]undec-7-en (DBU).

The process is known in general terms from for example ComprehensiveHeterocyclic Chemistry, A. R. Katritzky and C. W. Rees, Pergamon Press,Oxford, New York, 1984, Vol. 3; Part 2B; ISBN 0-08-030703-5, S. 482.

According to a further feature of the present invention where one of R⁴or R⁵ in, formula (I) is (C₁-C₄)alkyl, (C₁-C₄)haloalkyl, (C₃-C₄)alkenyl,(C₃-C₄)haloalkenyl, (C₃-C₄)alkynyl or (C₃-C₄)haloalkynyl, inventioncompounds of formula (I) may be prepared by the reaction of thecorresponding compound of formula (I) wherein said R⁴ or R⁵ respectivelyis H, and the other radicals and the configurations are as defined informula (I), with an alkylating agent of formula (VI) or (VII)respectively:

R⁴-L²  (VI)

R⁵-L²  (VII)

wherein L² is a leaving group, generally halogen, preferably chlorine,bromine or iodine, or an alkyl- or phenyl-sulfonyloxy moiety such asmethyl sulfonyloxy or 4-toluenesulfonyloxy. The reaction is generallyperformed in an inert solvent such as tetrahydrofuran, dioxan,acetonitrile or N,N-dimethylformamide at a temperature of from 0° C. tothe reflux temperature of the solvent; preferably at 20° C. to 100° C.

According to a further feature of the present invention compounds offormula (I), wherein one of R⁴ or R⁵ is an acyl radical, may be preparedby the reaction of the corresponding compound of formula (I) whereinsaid R⁴ or R⁵ respectively is H, and the other radicals and theconfigurations are as defined in formula (I), with an acylating agent offormula (VIII) or (IX) respectively:

R⁴-L³  (VIII)

R⁵-L³  (IX)

wherein R⁴ and R⁵ are each an acyl radical as defined in formula (I) andL³ is a leaving group, generally halogen, preferably chlorine; or with aformylating agent such as formic acid-acetic anhydride. A base isoptionally used for the acylation reaction and is generally chosen froman alkali metal hydroxide, alkali metal hydride, alkali metal carbonate,alkali metal alkoxide, alkaline earth metal carbonate, or an organicbase such as a tertiary amine for example triethylamine.

The reaction is generally performed in an inert solvent such astetrahydrofuran, dioxan, acetonitrile or N,N-dimethylformamide at atemperature of from 0° C. to the reflux temperature of the solvent,preferably at 20° C. to 100° C.

Intermediates of formula (III) may be prepared by the reaction of acompound of formula (X):

with a compound of said formula (V). The reaction is generally performedusing an acid addition salt, for example the hydrochloride salt of thecompound of formula (X), in a solvent such as 1,2-dichlorobenzene,decalin or white mineral oil, at a temperature of from 20° C. to thereflux temperature of the solvent, preferably at 50° C. to 200° C.

Intermediates of formula (V) may be prepared according to known methods,for example by the reductive amination, optionally asymmetric reductiveamination, of ketones of formula (XI) or the corresponding oximes:

in which R⁶, R⁷, R⁸, R⁹, R¹⁰ and A are as defined in formula (I), or thereaction of compounds of formula (XII):

in which

R⁶, R⁷, R⁸, R⁹, R¹⁰ and A are as defined in formula (I) and L⁴ is aleaving group such as halogen, hydroxy, methyl sulfonyloxy or4-toluenesulfonyloxy, with ammonia or a salt thereof, according to knownprocedures for example as described in patent publication number WO97/031904.

For the preparation of compounds of formula (I), in which one or moreasymmetric carbon atoms is present as a single enantiomeric form, theabove processes can be adapted, by employing the appropriateenantiomeric or diastereomeric form of the compounds of formula (II),(III), (IV), (V), (VI), (VII) or (XII).

Compounds of formula (II) in an, enantiomerically pure form are known orcan be prepared according to known procedures, for example as describedin Tetrahedron Asymmetry 1994, 5, 981, J. Chem. Soc. Perkin Trans I,1979, 2248 and the literature cited therein.

The preparation of compounds of formula (I) in resolved form orpartially resolved form may, for example, be carried out by followingthe above-defined processes using one or more intermediates (II), (III),(IV) or (V) whose configuration differs from the configuration asdefined, in the compound of formula (I) to be prepared, and resolvingthe mixture obtained according to known methods of resolution.

It is generally possible to use customary methods for opticalresolutions (cf. Textbooks of Stereochemistry), for example followingprocesses for separating mixtures into diastereomers, for examplephysical processes, such as crystallization, chromatographic processes,in particular, column chromatography and high pressure liquidchromatography, distillation, if appropriate under reduced pressure,extraction and other processes, it is possible to separate the remainingmixtures of enantiomers, generally by chromatographic separation onchiral solid phases. Suitable for preparative amounts or use on anindustrial scale are processes such as the crystallization ofdiastereomeric salts which can be obtained from the compounds (I) usingoptically active acids and, if appropriate, provided that acidic groupsare present, using optically active bases.

Optically active acids which are suitable for optical resolution bycrystallization of diastereomeric salts are, for example,camphorsulfonic acid, camphoric acid, bromocamphorsulfonic acid, quinicacid, tartaric acid, dibenzoyltartaric acid and other analogous acids;suitable optically active bases are, for example, quinine, cinchonine,quinidine, brucine, 1-phenylethylamine and other analogous bases.

The crystallizations are then in most cases carried out in aqueous oraqueous-organic solvents, where the diastereomer which is less solubleprecipitates first, if appropriate after seeding. One enantiomer of thecompound of the formula (I) is then liberated from the precipitatedsalt, or the other is liberated from the crystals, by acidification orusing base.

Enantiomerically pure amine intermediates, of formula (V) may beprepared using known methods, for example as described in Houben-Weyl,Methoden der Organischen Chemie, 4. Auflage, Band E 21b, 1833 ff. orBand E 21e, 5133.

One of the preferred procedures is the reductive amination of ketones offormula (XI) with asymmetric catalysis, including enzymatictransamination. Another procedure for the preparation ofenantiomerically pure amines of formula (V), is the racemate cleavingmethod described in J. Prakt. Chem. 339, (1997), pages 381-384, or aprocedure described in Org. Lett., Vol. 3, Nr. 25, page 4101. In thisprocedure the racemic amine of the general formula (V) is acylatedenantioselectively with an acylating agent such as an optionallysubstituted fatty, acid ester (preferably methyl chloroacetate or ethylchloroacetate or methyl methoxyacetate or ethyl methoxyacetate) in thepresence of a biocatalyst. The non-acylated enantiomer is then separatedby simple treatment with mineral acid. The acylated amine enantiomer isthen cleaved back to the corresponding amine, using a base for examplean alkali metal hydroxide such as sodium hydroxide, or an acid, forexample a mineral acid such as hydrogen chloride.

As biocatalysts, lipases, for example Pseudomonas cepacia, Candidacylindracea or Candida antarctica, are particularly suitable for thispurpose. Certain of these lipases are also commercially available inimmobilized form (brand name: “Novozym 435”).

By analogy with said enzymatic acylation method the compounds of formula(XIII) or (XIV) can be prepared as intermediates by acylation of racemicamines corresponding to compounds of formula (V), in principle,

wherein R⁶, R⁷, R⁸, R⁹, R¹⁰ and A are as defined in formula (I), and

-   R¹¹ is acyl, preferably (C₁-C₆)alkanoyl which is unsubstituted or    substituted by one or more radicals selected from the group    consisting of halogen, (C₁-C₄)alkoxy and (C₁-C₄)alkylthio; more    preferably formyl, acetyl, propionyl, haloacetyl, halopropionyl,    (C₁-C₄)alkoxyacetyl or (C₁-C₄)alkoxypropionyl, most preferably    chloroacetyl or methoxyacetyl;    the desired optical isomer (V) is then obtained by cleaving    compound (XIII) by using mineral acid, or, in the case when acylated    compound (XIV) is formed enzymatically, using the non-acylated    amine (V) directly.

The following acids, for example, are suitable for preparing the acidaddition salts of the compounds of the formula (I): hydrohalic acids,such as hydrochloric acid or hydrobromic acid, furthermore phosphoricacid, nitric acid, sulfuric acid, mono- or bifunctional carboxylic acidsand hydroxycarboxylic acids, such as acetic acid, oxalic acid, maleicacid, succinic acid, fumaric acid, tartaric add, citric acid, salicylicacid, sorbic acid or lactic acid, and also sulfonic acids, such asp-toluenesulfonic acid and 1,5-naphthalenedisulfonic acid. The acidaddition compounds of the formula (I) can be obtained in a simple mannerby the customary methods for forming salts, for, example by dissolving acompound of the formula (I) in a suitable organic solvent, such as, forexample, methanol, acetone, methylene chloride or benzene, and, addingthe acid at temperatures from 0 to 100° C., and they can be isolated ina known manner, for example by filtration, and, if appropriate, purifiedby washing with an inert organic solvent.

The base addition salts of the compounds of the formula (I) arepreferably prepared in inert polar solvents such as, for example, water,methanol or acetone at temperature from 0 to 100° C. Examples ofsuitable bases for preparing the salts according to the invention arealkali metal carbonates, such as potassium carbonate, alkali metal andalkaline earth metal hydroxides, for example NaOH or KOH, alkali metaland alkaline earth metal hydrides, for example NaH, alkali metal andalkaline earth metal alkoxides, for example sodium methoxide, potassiumtert-butoxide, or ammonia or ethanolamine. Quaternary ammonium salts canbe obtained, for example, by salt exchange or condensation withquaternary ammonium salts of the formula [NRR′R″R″′]⁺X⁻ where R, R′, R″and R″′ independently of one another are (C₁-C₄)alkyl, phenyl or benzyland, X⁻ is an anion, for example Cl⁻ or OH⁻.

Some of the compounds of formula (III) and (V) in which one or moreasymmetric carbon atoms are present as a single or optically enrichedenantiomeric form are novel and as such form a further feature of theinvention, and may be prepared as described above. The following aminesof formula (V) are known:

a) indanes:

-   -   (1R)-1-amino-indane (Chem. Abstracts Registry No. 10277-74-4);    -   (1R)-1-amino-7-methoxy-indane (Arch. Pharm. 331 (1998) 59-71);    -   (1R)-1-amino-7-n-propoxy-indane (Arch. Pharm. 331 (1998) 59-71);    -   (1R)-1-amino-7-cyano-indane (Arch. Pharm. 331 (1998) 59-71);        b) tetrahydronaphthalenes:    -   (1R)-1-amino-1,2,3,4-tetrahydronaphthalene (Chem. Abstracts        Registry No. 23357-46-2);    -   (1R)-1-amino-7-methyl-1,2,3,4-tetrahydronaphthalene        (WO-98/47877);    -   (1R)-1-amino-7-methoxy-1,2,3,4-tetrahydronaphthalene        (WO-98/47877);    -   (1R)-1-amino-7-isopropyl-1,2,3,4-tetrahydronaphthalene        (WO-98/47877);    -   (1R)-1-amino-7-t-butyl-1,2,3,4-tetrahydronaphthalene        (WO-98/47877); hydrochloride salts of the latter two compounds        (WO-98/47877);    -   (1R)-1-amino-6,8-dimethyl-1,2,3,4-tetrahydronaphthalene (J. of        Chromatography 959 (2002) 75-83),        c) chromanes:    -   (4R)-4-amino-chromane (Beilstein Registry No. 7687402 and/or        7687403);

Therefore, a further feature of the invention thus relates to compoundsof formula (III) or (V), or salts thereof, wherein

R⁶ is H, (C₁-C₆)alkyl or (C₁-C₆)alkoxy;R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₄)alkyl,(C₁-C₃)haloalkyl, halogen, (C₁-C₃)alkoxy, (C₁-C₃)haloalkoxy or CN;A is CH₂, O or a direct bond; and wherein the stereochemicalconfiguration at the marked 1 position is as defined in formula (I),with the exception of compounds of formula (V), or salts thereof, where:

-   (i) A is a direct bond, R⁶, R⁷, R⁸ and R⁹ are each hydrogen, and R¹⁰    is hydrogen, methoxy, n-propoxy or cyano; or-   (ii) A is CH₂, and R⁶, R⁷, R⁸ and R¹⁰ are each hydrogen, and R⁹ is    hydrogen, methyl, methoxy, isopropoxy or t-butyl; or    -   A is CH₂, and R⁶, R⁷ and R⁹ are each hydrogen, and R⁸ is methyl        and R¹⁰ is methyl; or-   (iii) A is an oxygen atom, and R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each H.

A preferred class of novel intermediate compounds of formula (III) and(V), or salts thereof, are those wherein:

R⁶, R⁷ and R¹⁰ are each independently H or methyl;R⁸ is H, methyl, Cl or F;R⁹ is H, methyl, Cl, F or Br; andA is a direct bond, CH₂ or O; and the stereochemical configuration atthe marked 1 and position is as defined in formula (I),with the exception of compounds of formula (V), or salts thereof, where:

-   (i) A is a direct bond, R⁶, R⁷, R⁸ and R⁹ are each hydrogen, and R¹⁰    is hydrogen, or-   (ii) A is CH₂, and R⁶, R⁷, R⁸ and R¹⁰ are each hydrogen, and R⁹ is    hydrogen or methyl, or-   (iii) A is an oxygen atom, and R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each H.

A more preferred class of novel intermediate compounds of formula (III)and (V), or salts thereof, are those wherein:

A is a direct bond,R⁶ is H or methyl;R⁷ and R¹⁰ are hydrogen,R⁸ is H, methyl, Cl or F;R⁹ is methyl, Cl, F or Br; andthe stereochemical configuration at the marked 1 and position is asdefined in formula (I).

Further preferred classes of novel intermediate compounds of formula(Va) and (Vb), or salts thereof:

wherein:R⁶ is methyl;R⁷ and R¹⁰ are each independently H or methyl;R⁸ is H, methyl, Cl or F;R⁹ is H, methyl, Cl, F or Br; andA is a direct bond, CH₂ or O; and as such form a further feature of theinvention.

Some of the compounds of formula (XIII) (amides) which can be used asintermediates for the preparation of the optically active amines formula(V) or biguanides of formula (III) in which one or more asymmetriccarbon atoms are present as a single or optically enriched enantiomericform are novel and as such form a further feature of the invention, andmay be prepared as described above. The following acylated amines offormula (XIII) are already known:

a) indanes

-   -   (1R)-1-acetylamino-indane (Chem. Europe 6 (2000, 1840-1846);    -   (1R)-1-formylamino-indane (J. Am. Chem. Soc. 88 (1966)        2233-2240)    -   (1R)-1-(trifluoroacetylamino)-indane (J. Med. Chem. 45 (2002)        5260-5279 or U.S. Pat. No. 4,948,395)    -   (1R)-1-(bromoacetylamino)-indane (Biochemistry 1980, 2140-2144);    -   (1R)-1-acetylamino-2-methyl-indane (J. Org. Chem. 1999,        1774-1775);    -   (1R)-1-acetylamino-5-fluoro-indane (J. Org. Chem. 1999,        1774-1775);        b) tetrahydronaphthalenes:    -   (1R)-1-acetylamino-1,2,3,4-tetrahydronaphthalene (J. Org. Chem.        1999, 1774-1775 or Tetrahedron Lett. 43 (2002) 5260);    -   (1R)-1-acetylamino-6-methoxy-1,2,3,4-tetrahydronaphthatene (J.        Org. Chem. 1999);    -   (1R)-1-acetylamino-5,7-dimethyl-1,2,3,4-tetrahydronaphthalene        (J. Org. Chem. 1999, 1774-1775);    -   (1R)-1-(chloroacetylamino)-1,2,3,4-tetrahydronaphthalene        (Farmaco. ED. Sci. Vol. 26 (1971) 474-486);    -   (1R)-1-(trifluoroacetylamino)-1,2,3,4-tetrahydronaphthalene        (U.S. Pat. No. 4,948,395);        c) chromanes:    -   (4R)-4-acetylamino-chromane (Org. Lett. 4 (2002) 1695-1668);

A further feature of the invention are thus novel compounds of formula(XIII) or salts thereof, wherein

R⁶ is H, (C₁-C₆)alkyl or (C₁-C₆)alkoxy;R⁷, R⁸, R⁹ and R¹⁰ are each independently H, (C₁-C₄)alkyl,(C₁-C₃)haloalkyl, halogen, (C₁-C₃)alkoxy, (C₁-C₃)haloalkoxy or CN;R¹¹ is acyl, preferably (C₁-C₆)alkanoyl which is unsubstituted orsubstituted by one or more radicals selected from the group consistingof halogen, (C₁-C₄)alkoxy and (C₁-C₄)alkylthio; more preferably formyl,acetyl, propionyl, haloacetyl, halopropionyl, (C₁-C₄)alkoxyacetyl or(C₁-C₄)alkoxypropionyl, most preferably chloroacetyl or methoxyacetyl;A is CH₂, O or a direct bond; and wherein the stereochemicalconfiguration at the marked 1 position is as defined in formula (I),with the exception of compounds, or salts thereof, where:

-   (i) A is a direct bond, R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each hydrogen,    and R¹¹ is formyl, acetyl, trifluoroacetyl or bromoacetyl, or    -   A is a direct bond, R⁶ is methyl; R⁷, R⁸, R⁹ and R¹⁰ are each        hydrogen, and R¹¹ is acetyl, or    -   A is a direct bond, R⁶; R⁷, R⁹ and R¹⁰ are each hydrogen, R⁸ is        fluoro, and R¹¹ is acetyl, or-   (ii) A is CH₂, and R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each hydrogen, and R¹¹    is acetyl, trifluoroacetyl or chloroacetyl; or    -   A is CH₂, and R⁶, R⁷ and R⁹ are each hydrogen, and R⁸ is methyl        and R¹⁰ is methyl; and R¹¹ is acetyl, or    -   A is CH₂, and R⁶, R⁷, R⁹ and R¹⁰ are each hydrogen, and R⁸ is        methoxy, and R¹¹ is acetyl, or    -   A is CH₂, and R⁶ is methyl, R⁷, R⁸, R⁹ and R¹⁰ are each        hydrogen, and R¹¹ is acetyl, or-   (iii) A is an oxygen atom, and R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each H,    and R¹¹ is acetyl.

Compounds of formula (II), (IV), (VI), (VII), (VIII), (IX), (X), (XI)and (XII), as well as racemic (III) and (V) are known or may be preparedanalogously to known methods.

A collection of compounds of formula (I) which can be synthesized by theabovementioned processes can additionally be prepared in parallelfashion, which can be effected manually, partly automated or fullyautomated. In this context, it is possible to automate the procedure ofthe reaction, work-up or purification of the products or intermediates.In total, this is to be understood as meaning a procedure which isdescribed, for example, by S. H. DeWitt in “Annual Reports inCombinatorial Chemistry and Molecular Diversity: Automated Synthesis”,Volume 1, published by Escom, 1997, pages 69 to 77.

For carrying out the reaction and work-up in parallel fashion, a seriesof commercially available apparatuses can be used as they are availablefrom for example, Stem Corporation, Woodrolfe Road, Tollesbury, Essex,CM9 8SE, England or H+P Labortechnik GmbH, Bruckmannring 28, 85764Oberschleissheim, Germany. To carry out the parallel purification ofcompounds (I) or of intermediates obtained during the preparation, thereare available, inter alia, chromatographic equipment, for example fromISCO, Inc., 4700 Superior Street, Lincoln, Nebr. 68504, USA. Theequipment mentioned makes possible a modular procedure, where theindividual steps are automated, but manual operation has to be carriedout between the steps. This can be circumvented by employing partly orfully integrated automation systems, in which the automation modules inquestion are operated by, for example, robots. Such automation systemscan be obtained from, for example, Zymark Corporation, Zymark Center,Hopkinton, Mass. 01748, USA.

In addition to the above-described methods, compounds of formula (I) canbe prepared in full or partly by solid-phase supported methods. To thisend, individual intermediates or all intermediates of the synthesis orof a synthesis adapted to the procedure in question are bound to asynthesis resin. Solid-phase supported synthetic methods are describedextensively in the specialist literature, for example: Barry A. Bunin in“The Combinatorial Index”, published by Academic Press, 1998.

The use of solid-phase supported synthesis methods permits a series ofprotocols known from the literature which, in turn, can be carried outmanually or in an automated fashion. For example, the “teabag method”(Houghten, U.S. Pat. No. 4,631,211; Houghten et al., Proc. Natl. Acad.Sci., 1985, 82, 5131-5135) can be partly automated with products ofIRORI, 11149 North Torrey Pines Road, La Jolla, Calif. 92037, USA.Solid-phase supported parallel synthesis can be automated successfullyfor example using equipment by Argonaut Technologies, Inc., 887Industrial Road, San Carlos, Calif. 94070, USA or MultiSynTech GmbH,Wullener Feld 4, 58454 Witten, Germany.

The preparation in accordance with the processes described herein yieldscompounds of formula (I) in the form of substance collections orsubstance libraries. Subject matter of the present invention, are:therefore also libraries of the compounds of formula (I) which containat least two compounds of formula (I), and of their precursors.

The following non-limiting Examples illustrate the preparation of thecompounds of formula (I).

A. Chemical Examples

In the Examples which follow, quantities (also percentages) are weightbased unless stated otherwise. Ratios of solvents are volume based.

The optical rotation is measured as specific rotation [α] of thepolarized light of 589 nm wavelength (polarized Na-D light) understandard conditions (c=1 g/ml, t=25° C.). The solvent is chloroformunless indicated otherwise.

Example A1 2-Amino-4-[(1R)-1-indanylamino]-6-methyl-1,3,5-triazine(Table 8, Compound Number 8.1)

A mixture of 2-amino-4-chloro-6-methyl-1,3,5-triazine (2.2 g, 0.015mol), R(−)-1-aminoindane (2.0 g, 0.015 mol) and potassium carbonate (4.6g, 2.2 mol) in N,N-dimethylformamide was: stirred for 5 hours at 90-100°C. When the reaction was complete, the solvent was evaporated in vacuobelow 100° C., the mixture obtained was cooled and water was added.Ethyl acetate was added and the organic layer separated, dried (sodiumsulfate) and evaporated. The residue was purified by columnchromatography, eluting with ethyl acetate to give2-amino-4-[(1R)-1-indanylamino]-6-methyl-1,3,5-triazine (3.5 g, 95%yield, Compound number 8.1), mp. 94-96° C., chemical purity>95%, ee 91%by HPLC, optical rotation (CHCl₃, c=1): +87.4°).

Example A22-Amino-4-[(4R)-4-chromanylamino]-6-[(1R)-1-fluoroethyl]-1,3,5-triazineTable 1, Compound number 1.20) a. chroman-4-one oxime

A mixture of sodium acetate (41.53 g; 0.506 mol) in water at 60° C. wascombined with a stirred mixture of chroman-4-one (25 g, 0.169 mol) andhydroxylamine hydrochloride (20.0 g, 0.287 mol) in ethanol at 60° C. Theresulting mixture was heated at reflux for 90 minutes, cooled andfiltered. The crude solid was washed with water to give chroman-4-oneoxime (27.9 g, yield 96%), mp. 114-117° C., purity 95%.

b. 4-aminochromane hydrochloride

Chroman-4-one oxime (27.9 g, 0.157 mol) in ethanol was added toRaney-nickel catalyst (3.0 g) in ethanol under nitrogen. The mixture wasstirred and hydrogen introduced until the theoretical amount(approximately 3.6 l) was adsorbed. The catalyst was filtered, thesolvent evaporated and 6N ethanolic hydrochloric acid solution (25 ml)added. The solvent was evaporated and the residue washed withdiethylether/acetone (10:1) and refiltered to give 4-aminochromanehydrochloride (18.3 g, yield 58%), mp. 220-226° C., purity 95%.

c. N-[(4R)-4-chromanyl]-2-methoxyacetamide

A mixture of 4-aminochromane hydrochloride (27.8 g, 0.15 mol) andaqueous sodium hydroxide (2N) was extracted with ethyl acetate and theorganic layer dried (sodium sulfate) and evaporated to give racemic4-aminochromane (14.2 g, 0.095 mol). To this was added methyl2-methoxyacetate (10.94 g, 0.105 mol) and 2.5 g Novozym 435 (AldrichCorp.) in tert-butyl methyl ether, and the mixture heated at reflux for2 hours. A further addition of Novozym 435 (0.5 g) was made and heatingcontinued until the reaction was complete as judged by hplc.Dichloromethane was added, the biocatalyst filtered off and the organiclayer dried (sodium sulfate) and evaporated. The residue was dissolvedin the minimum of dichloromethane, and ethanolic hydrochloric acidsolution (8N) was added to give (4S)-4-aminochromane hydrochloride whichwas filtered off, and the filtrate evaporated to giveN-[(4R)-4-chromanyl]-2-methoxyacetamide (8.2 g), mp. 109-112° C.

d. (4R)-4-aminochromane hydrochloride

A solution of the above N-[(4R)-4-chromanyl]-2-methoxyacetamide (2.2 g,0.0325 mol) in ethanol (100 ml) and concentrated hydrochloric acid (30ml) was heated at reflux for 12 hours, then evaporated. A small amountof ethyl acetate was added to the residue and the solid filtered off togive (4R)-4-aminochromane hydrochloride (2.3 g), m.p. 261-263° C.,chemical purity>95%.

e. (4S)-4-(bisguanidino)chromane hydrochloride

A homogeneous mixture of (4R)-3,4-dihydro-2H-4-chromanylammoniumchloride (2.3 g, 0.0124 mol) and 1-cyanoguanidine (1.04 6, 0.0124 mol)in 1,3-dichlorobenzene was heated at 140-150° C. for 150 minutes. Thecooled mixture was diluted with toluene and filtered to give(4S)-4-(bisguanidino)chromane hydrochloride (3.3 g, yield 89.4%) as asolid, purity 90%.

f.2-amino-4-[(4R)-4-chromanylamino]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine

A 30% solution of sodium methoxide in methanol (0.7 g, 0.75 ml, 0.004mol) was added to a stirred suspension of (4S)-4-(bisguanidino)chromanehydrochloride (1.1 g, 0.004 mol) in methanol. Then methyl(2R)-2-fluoropropanoate (1.08 g, 0.01 mol) was added at roomtemperature, followed by an additional amount of a 30% solution ofsodium methoxide (1.0 g, 1.0 ml, 0.006 mol). After 4 hours at roomtemperature the mixture was filtered, the filtrate evaporated and theresidue dissolved in ethyl acetate. The organic phase was washed(water), dried (sodium sulfate) and evaporated. The residue was purifiedby column chromatography, eluting with a 7:3 mixture of ethylacetate:heptane to give2-amino-4-[(4R)-4-chromanylamino]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine(0.3 g, yield 25%, Compound number 1.20), m.p. 110-112° C., opticalrotation (dichloromethane, c=1): +75.4°, purity 98.35% (hplc, ChiralcelOD, 250×4.6 mm, eluent n-hexane:2-propanol 90:10, 0.6 ml/min, rt 21.4min.).

Example A32-Amino-4-[(1R,2S)-2-methyl-1-indanylamino]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine(Table 2, Compound Number 2.1) a. 2-methyl-indan-1-one oxime

A mixture of 2-methyl-1-indanone (10 g, 0.0684 mol) and hydroxylaminehydrochloride (9.5 g, 0.1368 mol) in ethanol was stirred at 60° C., anda solution of sodium acetate (16.8 g, 0.2052 mol) in water added. Theresulting mixture was then heated at reflux for 90 minutes, then cooledand the solid filtered. The crude product was washed with water andfiltered to give 2-methyl-indan-1-one oxime (9.9 g, yield 81%), mp.82-91° C., in 90% purity.

b. 1-(RS)(+−)-1-amino-2-methylindane hydrochloride

A mixture of the above 2-methylindan-1-one oxime (9.5 g, 0.0589 mol) andpalladium on, charcoal catalyst (10% 1.0 g) in methanol and acetic acidwas stirred under nitrogen. Hydrogen was then introduced until thetheoretical amount was adsorbed. The catalyst was filtered off and thesolvent; evaporated in vacuo. Ethanolic hydrochloric acid solution (6N)was added, the solvent evaporated and the residue washed with a mixtureof diethylether/acetone (10:1) and filtered to give1-(RS)(+−)-1-amino-2-methylindane hydrochloride (9.7 g, yield 85%), mp.241-242° C., purity 95%.

c. trans-1-amino-2-methylindane

1-(RS)(+−)-1-Amino-2-methylindane hydrochloride (19.7 g, 0.1073 mol) wasmixed with aqueous sodium hydroxide (2N) and extracted with ethylacetate. The organic layer is dried (sodium sulfate), evaporated, andthe residue purified by column chromatography, eluting with ethylacetate/triethylamine (100:1) to give the following compounds:

-   i) trans-1-amino-2-methylindane (6.6 g), ¹H-NMR (CDCl₃): 1.25 (3H,    d), 1.90-2.05 (1H, m), 2.5 (1H, dd), 3.05 (1H, dd), 3.78 (1H, d, 8.1    Hz), 7.1-7.3 (4H, m);-   ii) a mixture of trans-1-amino-2-methylindane and    cis-1-amino-2-methylindane (2.7 g); and-   iii) cis-1-amino-2-methylindane (4.0 g), ¹H-NMR (CDCl₃): 0.95 (3H,    d), 2.40-2.60 (2H, m), 2.80-2.95 (1H, m), 4.20 (1H, d, 6.2 Hz),    7.1-7.3 (4H, m).

d. N-[(1R,2S)-2-methyl-1-indanyl]-2-methoxyacetamide, and(1S,2R)-1-amino-2-methylindane hydrochloride

Novozym 435 (Aldrich Corp., 1.0 g) was added to a mixture oftrans-1-amino-2-methylindane (6.6 g, 0.0448) and methyl 2-methoxyacetate(5.04 g 0.0484 mol) in tert-butyl methyl ether. The mixture was heatedat reflux for 2 hours, a further amount of Novozym 435 (0.5 g) added andheating is continued for an additional 2 hours. Dichloromethane wasadded to the cooled mixture and the biocatalyst filtered off. Theorganic layer was dried (sodium sulfate), evaporated and the residuedissolved in the minimum of dichloromethane. A solution of ethanolichydrochloric acid (8N) was added and the solid filtered to give(1S,2R)-1-amino-2-methylindane hydrochloride, and the filtrateevaporated to give N-[(1R,2S)-2-methyl-1-indanyl]-2-methoxyacetamide(5.9 g), m.p. 78-79° C.

e. (1R,2S)-1-amino-2-methylindane hydrochloride

Concentrated hydrochloric acid (8 ml) was added to a solution ofN-[(1R,2S)-2-methyl-1-indanyl]-2-methoxyacetamide (5.9 g, 0.0269 mol) inethanol and water, and the mixture heated for 12 hours at reflux. Thesolvent was evaporated and a small amount of ethyl acetate added. Theundissolved solid was filtered off to give(1R,2S)-1-amino-2-methylindane hydrochloride (1.0 g) as a solid,chemical purity>95%.

f. (1R,2S)-1-(bisguanidino)-2-methylindane monohydrochloride

A homogeneous mixture of (1R,2S)-1-amino-2-methylindane hydrochloride(1.0 g, 0.0054 mol) and 1-cyanoguanidine (0.46 g, 0.0054 mol) in1,3-dichlorobenzene was heated for 150 minutes at 140-150° C. The cooledmixture was diluted with toluene and the solid filtered off to give(1R,2S)-1-(bisguanidino)-2-methylindane monohydrochloride (1.1 g, yield67.7%) as a solid, mp. 172-178° C., purity 90%.

g.2-amino-4-[(1R,2S)-2-methyl-1-indanylamino]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine

A 30% solution of sodium methoxide (0.39 g, 0.4 ml, 0.0022 mol) inmethanol was added to a stirred suspension of(1R,2S)-1-(bisguanidino)-2-methylindane monohydrochloride (0.550 g,0.0021 mol) in methanol. Then methyl (2R)-2-fluoropropanoate (0.55 g,0.0051 mol) was added at room temperature, followed by an additionalquantity of 30% solution of sodium methoxide (0.59 g, 0.6 ml, 0.0033mol). After 4 hours at room temperature the mixture was filtered, andthe filtrate evaporated. The residue was dissolved in ethyl acetate,washed (water), dried (sodium sulfate) and evaporated. The residue waspurified by column chromatography, eluting with a mixture of ethylacetate:heptane (7:3) as eluent to give2-amino-4-[(1R,2S)-2-methyl-1-indanylamino]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine(0.09 g, yield 15%, Compound number 2.1), mp. 146-150° C., opticalrotation (chloroform, c=1): +104.4°, purity 95.25% (hplc, Chiralcel OD,250×4.6 mm, eluent n-hexane:2-propanol 90:10, 0.6 ml/min, rt 17.93 min).

The following preferred compounds of formula (I) shown in Tables 1 to 14also form part of the present invention, and are obtained by, oranalogously to, the above Examples A1, A2 and A3 or the above-describedgeneral methods.

In the Tables the structure of a compound is represented by the formulaof the predominant stereochemical isomer unless defined otherwisespecifically (e.g. racemic mixture of chiral compounds).

The following abbreviations are used in the Tables 1 to 14:

“Me” means methyl, and “Et” means ethyl, and “Pr” means n-propyl.

“Cpd” means Compound Number. Compound numbers are given for referencepurposes only.

After the end of some Tables additional physical data are provided forsome of the compounds in the respective Table.

Optical rotation is measured and defined as for the examples A1 to A3above.

¹H-NMR spectra were recorded in deuterochloroform unless otherwisestated, with chemical shifts given in ppm. The following notations areused: s=singlet, d=doublet, t=triplet, m=multiplet.

TABLE 1 Compounds of formula (Id-1): (Id-1)

Cpd R¹ R³ R⁷ R⁸ R⁹ R¹⁰ A Physical data 1.1 Me F H H H H direct bondwhite solid 1.2 Me F H H Me H direct bond light brown solid 1.3 Me F H HF H direct bond white solid 1.4 Me F H H Cl H direct bond 1.5 Me F H HBr H direct bond 1.6 Me F Me H Me H direct bond 1.7 Me F H Me Me Hdirect bond waxy solid 1.8 Me F H H Me Me direct bond 1.9 Me F H F Me Hdirect bond 1.10 Me F H Cl Cl H direct bond 1.11 Me F H H H H CH₂ whitesolid 1.12 Me F H H Me H CH₂ solid 1.13 Me F H H F H CH₂ 1.14 Me F H HCl H CH₂ 1.15 Me F Me H Me H CH₂ white solid 1.16 Me F H Me Me H CH₂1.17 Me F H H Me Me CH₂ 1.18 Me F H F Me H CH₂ 1.19 Me F H Cl Cl H CH₂1.20 Me F H H H H O white solid 1.21 Me F H H Me H O solid 1.22 Me F H HF H O 1.23 Me F H H Cl H O 1.24 Me Cl H H H H direct bond white solid1.25 Me Cl H H Me H direct bond 1.26 Me Cl H H F H direct bond 1.27 MeCl H H Cl H direct bond 1.28 Me Cl H H H H CH₂ solid 1.29 Me Cl H H Me HCH₂ 1.30 Me Cl H H F H CH₂ 1.31 Me Cl H H H H O white solid 1.32 Me Cl HH Me H O 1.33 Me Cl H H F H O 1.34 Me Cl H H Cl H O 1.35 Et F H H H Hdirect bond 1.36 Et F H H Me H direct bond 1.37 Et F H H F H direct bond1.38 Et F H H Cl H direct bond 1.39 Et F H H Br H direct bond 1.40 Et ClH H H H direct bond 1.41 Et Cl H H Me H direct bond 1.42 Et Cl H H F Hdirect bond 1.43 Et Cl H H Cl H direct bond 1.44 Et Cl H H Br H directbond 1.45 Et F H H H H CH₂ 1.46 Et F H H Me H CH₂ 1.47 Et F H H F H CH₂1.48 Et F H H Cl H CH₂ 1.49 Et F H H Br H CH₂ 1.50 Et Cl H H H H CH₂1.51 Et Cl H H Me H CH₂ 1.52 Et Cl H H F H CH₂ 1.53 Et Cl H H Cl H CH₂1.54 Et Cl H H Br H CH₂ 1.55 Et F H H H H O 1.56 Et F H H Me H O 1.57 EtF H H F H O 1.58 Et F H H Cl H O 1.59 Et F H H Br H O 1.60 Et Cl H H H HO 1.61 Et Cl H H Me H O 1.62 Et Cl H H F H O 1.63 Et Cl H H Cl H O 1.64Et Cl H H Br H O 1.65 Me Cl Me H Me H CH₂ 1.66 Me F Me Me H H O whitesolid 1.67 Me F F H H H O solid 1.68 Me F H H Et H direct solid 1.69 MeF H H OMe H direct solid Notes to physical data in TABLE 1 (reference,is made to the compound no. in Table 1): Cpd. 1.1: mp 176-178° C.,optical rotation +116.7°; Cpd. 1.2: optical rotation +113.5°; Cpd. 1.3:optical rotation +112.7°; Cpd. 1.11: mp 151-154° C., optical rotation+111.1°; Cpd. 1.12: mp 68-72° C., optical rotation +76.8°; Cpd. 1.15: mp163-165° C., optical rotation +70.1°; Cpd. 1.20: mp 110-112° C., opticalrotation +75.4°; Cpd. 1.21: 127-130° C., optical rotation +52.3°; Cpd.1.24: mp 153-155° C., optical rotation +82.5°; Cpd. 1.28: mp 140-144°C., optical rotation +79.9°; Cpd. 1.31: mp 99-100° C., optical rotation+69.2°. Cpd. 1.66: optical rotation +112.7°; Cpd. 1.67: mp 88-95° C.,optical rotation +66.5°; Cpd. 1.68: mp 145-146° C., optical rotation+79.3°; Cpd. 1.69: mp 149-150° C., optical rotation +84.0°

TABLE 2 Compounds of formula (If-1) (If-1)

Cpd R¹ R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A Physical data 2.1 Me F Me H H H H directbond white solid 2.2 Me F Me H H Me H direct bond white foam 2.3 Me F MeH H F H direct bond 2.4 Me F Me H H Cl H direct bond white solid 2.5 MeF Me H H Br H direct bond 2.6 Me F Me Me H Me H direct bond 2.7 Me F MeH Me Me H direct bond 2.8 Me F Me H H Me Me direct bond 2.9 Me F Me H FMe H direct bond 2.10 Me F Me H Cl Cl H direct bond 2.11 Me F Me H H H HCH₂ white solid 2.12 Me F Me H H Me H CH₂ 2.13 Me F Me H H F H CH₂ 2.14Me F Me H H Cl H CH₂ 2.15 Me F Me Me H Me H CH₂ 2.16 Me F Me H Me Me HCH₂ 2.17 Me F Me H H Me Me CH₂ 2.18 Me F Me H F Me H CH₂ 2.19 Me F Me HCl Cl H CH₂ 2.20 Me F Me H H H H O 2.21 Me F Me H H Me H O 2.22 Me F MeH H F H O 2.23 Me F Me H H Cl H O 2.24 Me Cl Me H H H H direct bond 2.25Me Cl Me H H Me H direct bond solid 2.26 Me Cl Me H H F H direct bond2.27 Me Cl Me H H Cl H direct bond 2.28 Me Cl Me H H Me H CH₂ whitesolid 2.29 Me Cl Me H H H H CH₂ 2.30 Me Cl Me H H Me H CH₂ 2.31 Me Cl MeH H F H CH₂ 2.32 Me Cl Me H H Cl H CH₂ 2.33 Me Cl Me H H H H O 2.34 MeCl Me H H Me H O 2.35 Me Cl Me H H F H O 2.36 Me Cl Me H H Cl H O 2.37Et F Me H H H H direct bond 2.38 Et F Me H H Me H direct bond 2.39 Et FMe H H F H direct bond 2.40 Et F Me H H Cl H direct bond 2.41 Et F Me HH Br H direct bond 2.42 Et Cl Me H H H H direct bond 2.43 Et Cl Me H HMe H direct bond 2.44 Et Cl Me H H F H direct bond 2.45 Et Cl Me H H ClH direct bond 2.46 Et Cl Me H H Br H direct bond 2.47 Et F Me H H H HCH₂ 2.48 Et F Me H H Me H CH₂ 2.49 Et F Me H H F H CH₂ 2.50 Et F Me H HCl H CH₂ 2.51 Et F Me H H Br H CH₂ 2.52 Et Cl Me H H H H CH₂ 2.53 Et ClMe H H Me H CH₂ 2.54 Et Cl Me H H F H CH₂ 2.55 Et Cl Me H H Cl H CH₂2.56 Et Cl Me H H Br H CH₂ 2.57 Et F Me H H H H O 2.58 Et F Me H H Me HO 2.59 Et F Me H H F H O 2.60 Et F Me H H Cl H O 2.61 Et F Me H H Br H O2.62 Et Cl Me H H H H O 2.63 Et Cl Me H H Me H O 2.64 Et Cl Me H H F H O2.65 Et Cl Me H H Cl H O 2.66 Et Cl Me H H Br H O 2.67 Me F Me Me Me H HO 2.68 Me F Me F H H H O 2.69 Me F Me H H Et H direct 2.70 Me F Me H HOMe H direct Notes to physical data in Table 2 (reference is made to thecompound no. in Table 2): Cpd. 2.1: mp 146-150° C., optical rotation+104°; Cpd. 2.11: optical rotation +168.9°; Cpd. 2.25: mp 68-70° C.,optical rotation +140.9°. Cpd. 2.28: mp 127-128° C., optical rotation+49.6°.

TABLE 3 Compounds of formula (Ie-1): (Ie-f)

Cpd R¹ R³ R⁷ R⁸ R⁹ R¹⁰ A Physical data 3.1 Me F H H H H direct bondwhite solid 3.2 Me F H H Me H direct bond white solid 3.3 Me F H H F Hdirect bond 3.4 Me F H H Cl H direct bond 3.5 Me F H H Br H direct bond3.6 Me F Me H Me H direct bond 3.7 Me F H Me Me H direct bond Waxy solid3.8 Me F H H Me Me direct bond 3.9 Me F H F Me H direct bond 3.10 Me F HCl Cl H direct bond 3.11 Me F H H H H CH₂ white solid 3.12 Me F H H Me HCH₂ 3.13 Me F H H F H CH₂ 3.14 Me F H H Cl H CH₂ 3.15 Me F Me H Me H CH₂white solid 3.16 Me F H Me Me H CH₂ 3.17 Me F H H Me Me CH₂ 3.18 Me F HF Me H CH₂ 3.19 Me F H Cl Cl H CH₂ 3.20 Me F H H H H O white solid 3.21Me F H H Me H O 3.22 Me F H H F H O 3.23 Me F H H Cl H O 3.24 Me Cl H HH H direct bond white solid 3.25 Me Cl H H Me H direct bond 3.26 Me Cl HH F H direct bond 3.27 Me Cl H H Cl H direct bond 3.28 Me Cl H H H H CH₂3.29 Me Cl H H Me H CH₂ 3.30 Me Cl H H F H CH₂ 3.31 Me Cl Me H Me H CH₂3.32 Me Cl H H H H O 3.33 Me Cl H H Me H O 3.34 Me Cl H H F H O 3.35 MeCl H H Cl H O 3.36 Et F H H H H direct bond 3.37 Et F H H Me H directbond 3.38 Et F H H F H direct bond 3.39 Et F H H Cl H direct bond 3.40Et F H H Br H direct bond 3.41 Et Cl H H H H direct bond 3.42 Et Cl H HMe H direct bond 3.43 Et Cl H H F H direct bond 3.44 Et Cl H H Cl Hdirect bond 3.45 Et Cl H H Br H direct bond 3.46 Et F H H H H CH₂ 3.47Et F H H Me H CH₂ 3.48 Et F H H F H CH₂ 3.49 Et F H H Cl H CH₂ 3.50 Et FH H Br H CH₂ 3.51 Et Cl H H H H CH₂ 3.52 Et Cl H H Me H CH₂ 3.53 Et Cl HH F H CH₂ 3.54 Et Cl H H Cl H CH₂ 3.55 Et Cl H H Br H CH₂ 3.56 Et F H HH H O 3.57 Et F H H Me H O 3.58 Et F H H F H O 3.59 Et F H H Cl H O 3.60Et F H H Br H O 3.61 Et Cl H H H H O 3.62 Et Cl H H Me H O 3.63 Et Cl HH F H O 3.64 Et Cl H H Cl H O 3.65 Et Cl H H Br H O Notes to physicaldata in Table 3 (reference is made to the compound no. in Table 3): Cpd3.1: mp 149-150° C., optical rotation +74.4°; Cpd 3.2: optical rotation+113.5°; Cpd 3.11: mp 147-149° C., optical rotation +84.4°; Cpd 3.15: mp167-171° C., optical rotation +36.5°; Cpd 3.20: mp 183-185° C., opticalrotation +54.5°; Cpd 3.24: mp 151-152° C., optical rotation +71.8°.

TABLE 4 Compounds of formula (Ig-1): (Ig-1)

Cpd R¹ R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A Physical data 4.1 Me F Me H H H H directbond white solid 4.2 Me F Me H H Me H direct bond white foam 4.3 Me F MeH H F H direct bond 4.4 Me F Me H H Cl H direct bond 4.5 Me F Me H H BrH direct bond 4.6 Me F Me Me H Me H direct bond 4.7 Me F Me H Me Me Hdirect bond 4.8 Me F Me H H Me Me direct bond 4.9 Me F Me H F Me Hdirect bond 4.10 Me F Me H Cl Cl H direct bond 4.11 Me F Me H H H H CH₂4.12 Me F Me H H Me H CH₂ 4.13 Me F Me H H F H CH₂ 4.14 Me F Me H H Cl HCH₂ 4.15 Me F Me Me H Me H CH₂ 4.16 Me F Me H Me Me H CH₂ 4.17 Me F Me HH Me Me CH₂ 4.18 Me F Me H F Me H CH₂ 4.19 Me F Me H Cl Cl H CH₂ 4.20 MeF Me H H H H O 4.21 Me F Me H H Me H O 4.22 Me F Me H H F H O 4.23 Me FMe H H Cl H O 4.24 Me Cl Me H H H H direct bond 4.25 Me Cl Me H H Me Hdirect bond 4.26 Me Cl Me H H F H direct bond 4.27 Me Cl Me H H Cl Hdirect bond 4.28 Me Cl Me H H H H CH₂ 4.29 Me Cl Me H H Me H CH₂ 4.30 MeCl Me H H F H CH₂ 4.31 Me Cl Me H H Cl H CH₂ 4.32 Me Cl Me H H H H O4.33 Me Cl Me H H Me H O 4.34 Me Cl Me H H F H O 4.35 Me Cl Me H H Cl HO 4.36 Et F Me H H H H direct bond 4.37 Et F Me H H Me H direct bond4.38 Et F Me H H F H direct bond 4.39 Et F Me H H Cl H direct bond 4.40Et F Me H H Br H direct bond 4.41 Et Cl Me H H H H direct bond 4.42 EtCl Me H H Me H direct bond 4.43 Et Cl Me H H F H direct bond 4.44 Et ClMe H H Cl H direct bond 4.45 Et Cl Me H H Br H direct bond 4.46 Et F MeH H H H CH₂ 4.47 Et F Me H H Me H CH₂ 4.48 Et F Me H H F H CH₂ 4.49 Et FMe H H Cl H CH₂ 4.50 Et F Me H H Br H CH₂ 4.51 Et Cl Me H H H H CH₂ 4.52Et Cl Me H H Me H CH₂ 4.53 Et Cl Me H H F H CH₂ 4.54 Et Cl Me H H Cl HCH₂ 4.55 Et Cl Me H H Br H CH₂ 4.56 Et F Me H H H H O 4.57 Et F Me H HMe H O 4.58 Et F Me H H F H O 4.59 Et F Me H H Cl H O 4.60 Et F Me H HBr H O 4.61 Et Cl Me H H H H O 4.62 Et Cl Me H H Me H O 4.63 Et Cl Me HH F H O 4.64 Et Cl Me H H Cl H O 4.65 Et Cl Me H H Br H O Notes tophysical data in Table 4 (reference is made to the compound no. in Table4): Cpd. 4.1: mp 146-150° C., optical rotation +77.9°.

TABLE 5 Compounds of formula (Ih-1): (Ih-1)

Cpd R¹ R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A Physical data 5.1 Me F Me H H H H directbond waxy 5.2 Me F Me H H Me H direct bond yellow syrup 5.3 Me F Me H HF H direct bond 5.4 Me F Me H H Cl H direct bond 5.5 Me F Me H H Br Hdirect bond 5.6 Me F Me Me H Me H direct bond 5.7 Me F Me H Me Me Hdirect bond 5.8 Me F Me H H Me Me direct bond 5.9 Me F Me H F Me Hdirect bond 5.10 Me F Me H Cl Cl H direct bond 5.11 Me F Me H H H H CH₂5.12 Me F Me H H Me H CH₂ 5.13 Me F Me H H F H CH₂ 5.14 Me F Me H H Cl HCH₂ 5.15 Me F Me Me H Me H CH₂ 5.16 Me F Me H Me Me H CH₂ 5.17 Me F Me HH Me Me CH₂ 5.18 Me F Me H F Me H CH₂ 5.19 Me F Me H Cl Cl H CH₂ 5.20 MeF Me H H H H O 5.21 Me F Me H H Me H O 5.22 Me F Me H H F H O 5.23 Me FMe H H Cl H O 5.24 Me Cl Me H H H H direct bond 5.25 Me Cl Me H H Me Hdirect bond 5.26 Me Cl Me H H F H direct bond 5.27 Me Cl Me H H Cl Hdirect bond 5.28 Me Cl Me H H H H CH₂ 5.29 Me Cl Me H H Me H CH₂ 5.30 MeCl Me H H F H CH₂ 5.31 Me Cl Me H H Cl H CH₂ 5.32 Me Cl Me H H H H O5.33 Me Cl Me H H Me H O 5.34 Me Cl Me H H F H O 5.35 Me Cl Me H H Cl HO 5.36 Et F Me H H H H direct bond 5.37 Et F Me H H Me H direct bond5.38 Et F Me H H F H direct bond 5.39 Et F Me H H Cl H direct bond 5.40Et F Me H H Br H direct bond 5.41 Et Cl Me H H H H direct bond 5.42 EtCl Me H H Me H direct bond 5.43 Et Cl Me H H F H direct bond 5.44 Et ClMe H H Cl H direct bond 5.45 Et Cl Me H H Br H direct bond 5.46 Et F MeH H H H CH₂ 5.47 Et F Me H H Me H CH₂ 5.48 Et F Me H H F H CH₂ 5.49 Et FMe H H Cl H CH₂ 5.50 Et F Me H H Br H CH₂ 5.51 Et Cl Me H H H H CH₂ 5.52Et Cl Me H H Me H CH₂ 5.53 Et Cl Me H H F H CH₂ 5.54 Et Cl Me H H Cl HCH₂ 5.55 Et Cl Me H H Br H CH₂ 5.56 Et F Me H H H H O 5.57 Et F Me H HMe H O 5.58 Et F Me H H F H O 5.59 Et F Me H H Cl H O 5.60 Et F Me H HBr H O 5.61 Et Cl Me H H H H O 5.62 Et Cl Me H H Me H O 5.63 Et Cl Me HH F H O 5.64 Et Cl Me H H Cl H O 5.65 Et Cl Me H H Br H O

TABLE 6 Compounds of formula (Ii-1): (Ii-1)

Cpd R¹ R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A Physical data 6.1 Me F Me H H H H directbond wax 6.2 Me F Me H H Me H direct bond colourless syrup 6.3 Me F Me HH F H direct bond 6.4 Me F Me H H Cl H direct bond 6.5 Me F Me H H Br Hdirect bond 6.6 Me F Me Me H Me H direct bond 6.7 Me F Me H Me Me Hdirect bond 6.8 Me F Me H H Me Me direct bond 6.9 Me F Me H F Me Hdirect bond 6.10 Me F Me H Cl Cl H direct bond 6.11 Me F Me H H H H CH₂6.12 Me F Me H H Me H CH₂ 6.13 Me F Me H H F H CH₂ 6.14 Me F Me H H Cl HCH₂ 6.15 Me F Me Me H Me H CH₂ 6.16 Me F Me H Me Me H CH₂ 6.17 Me F Me HH Me Me CH₂ 6.18 Me F Me H F Me H CH₂ 6.19 Me F Me H Cl Cl H CH₂ 6.20 MeF Me H H H H O 6.21 Me F Me H H Me H O 6.22 Me F Me H H F H O 6.23 Me FMe H H Cl H O 6.24 Me Cl Me H H H H direct bond 6.25 Me Cl Me H H Me Hdirect bond 6.26 Me Cl Me H H F H direct bond 6.27 Me Cl Me H H Cl Hdirect bond 6.28 Me Cl Me H H H H CH₂ 6.29 Me Cl Me H H Me H CH₂ 6.30 MeCl Me H H F H CH₂ 6.31 Me Cl Me H H Cl H CH₂ 6.32 Me Cl Me H H H H O6.33 Me Cl Me H H Me H O 6.34 Me Cl Me H H F H O 6.35 Me Cl Me H H Cl HO 6.36 Et F Me H H H H direct bond 6.37 Et F Me H H Me H direct bond6.38 Et F Me H H F H direct bond 6.39 Et F Me H H Cl H direct bond 6.40Et F Me H H Br H direct bond 6.41 Et Cl Me H H H H direct bond 6.42 EtCl Me H H Me H direct bond 6.43 Et Cl Me H H F H direct bond 6.44 Et ClMe H H Cl H direct bond 6.45 Et Cl Me H H Br H direct bond 6.46 Et F MeH H H H CH₂ 6.47 Et F Me H H Me H CH₂ 6.48 Et F Me H H F H CH₂ 6.49 Et FMe H H Cl H CH₂ 6.50 Et F Me H H Br H CH₂ 6.51 Et Cl Me H H H H CH₂ 6.52Et Cl Me H H Me H CH₂ 6.53 Et Cl Me H H F H CH₂ 6.54 Et Cl Me H H Cl HCH₂ 6.55 Et Cl Me H H Br H CH₂ 6.56 Et F Me H H H H O 6.57 Et F Me H HMe H O 6.58 Et F Me H H F H O 6.59 Et F Me H H Cl H O 6.60 Et F Me H HBr H O 6.61 Et Cl Me H H H H O 6.62 Et Cl Me H H Me H O 6.63 Et Cl Me HH F H O 6.64 Et Cl Me H H Cl H O 6.65 Et Cl Me H H Br H O

TABLE 7 Compounds of formula (Ij-1): (Ij-1)

[In the compounds of formula (Ij-1) the marked 1* carbon atom isachiral] Physical Cpd R¹ R² R³ R⁷ R⁸ R⁹ R¹⁰ A data 7.1 H H H H H H Hdirect bond white solid 7.2 H H H H H Me H direct bond solid 7.3 H H H HH F H direct bond waxy 7.4 H H H H H Cl H direct bond waxy 7.5 H H H H HBr H direct bond 7.6 H H H Me H Me H direct bond 7.7 H H H H Me Me Hdirect bond 7.8 H H H H H Me Me direct bond 7.9 H H H H F Me H directbond 7.10 H H H H Cl Cl H direct bond 7.11 H H H H H H H CH₂ white solid7.12 H H H H H Me H CH₂ 7.13 H H H H H F H CH₂ 7.14 H H H H H Cl H CH₂7.15 H H H Me H Me H CH₂ 7.16 H H H H Me Me H CH₂ 7.17 H H H H H Me MeCH₂ 7.18 H H H H F Me H CH₂ 7.19 H H H H Cl Cl H CH₂ 7.20 H H H H H H HO 7.21 H H H H H Me H O 7.22 H H H H H F H O 7.23 H H H H H Cl H O 7.24Me Me H H H H H direct bond white solid 7.25 Me Me H H H Me H directbond 7.26 Me Me H H H F H direct bond 7.27 Me Me H H H Cl H direct bond7.28 Me H H H H Br H direct bond 7.29 Me H H Me H Me H direct bond 7.30Me H H H Me Me H direct bond 7.31 Me H H H H Me Me direct bond 7.32 Me HH H F Me H direct bond 7.33 Me H H H Cl Cl H direct bond 7.34 Me Me H HH H H CH₂ 7.35 Me Me H H H Me H CH₂ 7.36 Me Me H H H F H CH₂ 7.37 Me MeH H H Cl H CH₂ 7.38 Me H H Me H Me H CH₂ 7.39 Me H H H Me Me H CH₂ 7.40Me H H H H Me Me CH₂ 7.41 Me H H H F Me H CH₂ 7.42 Me H H H Cl Cl H CH₂7.43 Me Me H H H H H O 7.44 Me Me H H H Me H O 7.45 Me Me H H H F H O7.46 Me Me H H H Cl H O 7.47 Et H H H H H H direct bond white solid 7.48Et H H H H Me H direct bond white solid 7.49 Et H H H H F H direct bond7.50 Et H H H H Cl H direct bond 7.51 Et H H H H Br H direct bond 7.52Et H H Me H Me H direct bond 7.53 Et H H H Me Me H direct bond 7.54 Et HH H H Me Me direct bond 7.55 Et H H H F Me H direct bond 7.56 Et H H HCl Cl H direct bond 7.57 Et H H H H H H CH₂ white solid 7.58 Et H H H HMe H CH₂ 7.59 Et H H H H F H CH₂ 7.60 Et H H H H Cl H CH₂ 7.61 Et H H MeH Me H CH₂ 7.62 Et H H H Me Me H CH₂ 7.63 Et H H H H Me Me CH₂ 7.64 Et HH H F Me H CH₂ 7.65 Et H H H Cl Cl H CH₂ 7.66 Et H H H H H H O 7.67 Et HH H H Me H O 7.68 Et H H H H F H O 7.69 Et H H H H Cl H O 7.70 OMe H H HH H H direct bond white solid 7.71 OMe H H H H H H CH₂ 7.72 OMe H H H HMe H direct bond solid 7.73 OMe H H H H Me H CH₂ 7.74 Me H H H H H Hdirect bond white solid 7.75 Me H H H H Me H direct bond white solid7.76 Me H H H H F H direct bond 7.77 Me H H H H Cl H direct bond 7.78 MeH H H H H H CH₂ white solid 7.79 Me H H H H Me H CH₂ 7.80 Me H H H H F HCH₂ 7.81 Me H H H H Cl H CH₂ 7.82 Me H H H H H H O 7.83 Me H H H H Me HO 7.84 Me H H H H F H O 7.85 Me H H H H Cl H O 7.86 Cl Me Cl H H H Hdirect bond 7.87 Cl Me Cl H H Me H direct bond 7.88 Cl Me Cl H H F Hdirect bond 7.89 Cl Me Cl H H Cl H direct bond 7.90 Cl Me Cl H H H H CH₂7.91 Cl Me Cl H H Me H CH₂ 7.92 Cl Me Cl H H F H CH₂ 7.93 Cl Me Cl H HCl H CH₂ 7.94 Cl Me Cl H H H H O 7.95 Cl Me Cl H H Me H O 7.96 Cl Me ClH H F H O 7.97 Cl Me Cl H H Cl H O 7.98 H H F H H H H direct bond 7.99 HH F H H Me H direct bond 7.100 H H F H H F H direct bond 7.101 H H F H HCl H direct bond 7.102 H H F H H Br H direct bond 7.103 H H F Me H Me Hdirect bond 7.104 H H F H Me Me H direct bond 7.105 H H F H H Me Medirect bond 7.106 H H F H F Me H direct bond 7.107 H H F H Cl Cl Hdirect bond 7.108 H H F H H H H CH₂ 7.109 H H F H H Me H CH₂ 7.110 H H FH H F H CH₂ 7.111 H H F H H Cl H CH₂ 7.112 H H F Me H Me H CH₂ 7.113 H HF H Me Me H CH₂ 7.114 H H F H H Me Me CH₂ 7.115 H H F H F Me H CH₂ 7.116H H F H Cl Cl H CH₂ 7.117 H H F H H H H O 7.118 H H F H H Me H O 7.119 HH F H H F H O 7.120 H H F H H Cl H O 7.121 H H Cl H H H H direct bond7.122 H H Cl H H Me H direct bond 7.123 H H Cl H H F H direct bond 7.124H H Cl H H Cl H direct bond 7.125 H H Cl H H H H CH₂ 7.126 H H Cl H H MeH CH₂ 7.127 H H Cl H H F H CH₂ 7.128 H H Cl H H Cl H CH₂ 7.129 H H Cl HH H H O 7.130 H H Cl H H Me H O 7.131 H H Cl H H F H O 7.132 H H Cl H HCl H O 7.133 cyclopropyl H H H H H direct bond 7.134 cyclopropyl H H HMe H direct bond 7.135 cyclopropyl H H H F H direct bond 7.136cyclopropyl H H H Cl H direct bond 7.137 cyclopropyl H H H Br H directbond 7.138 cyclopropyl H Me H Me H direct bond 7.139 cyclopropyl H H MeMe H direct bond 7.140 cyclopropyl H H H Me Me direct bond 7.141cyclopropyl H H F Me H direct bond 7.142 cyclopropyl H H Cl Cl H directbond 7.143 cyclopropyl H H H H H CH₂ 7.144 cyclopropyl H H H Me H CH₂7.145 cyclopropyl H H H F H CH₂ 7.146 cyclopropyl H H H Cl H CH₂ 7.147cyclopropyl H Me H Me H CH₂ 7.148 cyclopropyl H H Me Me H CH₂ 7.149cyclopropyl H H H Me Me CH₂ 7.150 cyclopropyl H H F Me H CH₂ 7.151cyclopropyl H H Cl Cl H CH₂ 7.152 cyclopropyl H H H H H O 7.153cyclopropyl H H H Me H O 7.154 cyclopropyl H H H F H O 7.155 cyclopropylH H H Cl H O 7.156 cyclopropyl Me H H H H direct bond 7.157 cyclopropylMe H H Me H direct bond 7.158 cyclopropyl Me H H F H direct bond 7.159cyclopropyl Me H H Cl H direct bond 7.160 cyclopropyl Me H H H H CH₂7.161 cyclopropyl Me H H Me H CH₂ 7.162 cyclopropyl Me H H F H CH₂ 7.163cyclopropyl Me H H Cl H CH₂ 7.164 cyclopropyl Me H H H H O 7.165cyclopropyl Me H H Me H O 7.166 cyclopropyl Me H H F H O 7.167cyclopropyl Me H H Cl H O 7.168 cyclopropyl F H H H H direct bond 7.169cyclopropyl F H H Me H direct bond 7.170 cyclopropyl F H H F H directbond 7.171 cyclopropyl F H H Cl H direct bond 7.172 cyclopropyl F H H BrH direct bond 7.173 cyclopropyl F Me H Me H direct bond 7.174cyclopropyl F H Me Me H direct bond 7.175 cyclopropyl F H H Me Me directbond 7.176 cyclopropyl F H F Me H direct bond 7.177 cyclopropyl F H ClCl H direct bond 7.178 cyclopropyl F H H H H CH₂ 7.179 cyclopropyl F H HMe H CH₂ 7.180 cyclopropyl F H H F H CH₂ 7.181 cyclopropyl F H H Cl HCH₂ 7.182 cyclopropyl F Me H Me H CH₂ 7.183 cyclopropyl F H Me Me H CH₂7.184 cyclopropyl F H H Me Me CH₂ 7.185 cyclopropyl F H F Me H CH₂ 7.186cyclopropyl F H Cl Cl H CH₂ 7.187 cyclopropyl F H H H H O 7.188cyclopropyl F H H Me H O 7.189 cyclopropyl F H H F H O 7.190 cyclopropylF H H Cl H O 7.191 cyclopropyl Cl H H H H direct bond 7.192 cyclopropylCl H H Me H direct bond 7.193 cyclopropyl Cl H H F H direct bond 7.194cyclopropyl Cl H H Cl H direct bond 7.195 cyclopropyl Cl H H H H CH₂7.196 cyclopropyl Cl H H Me H CH₂ 7.197 cyclopropyl Cl H H F H CH₂ 7.198cyclopropyl Cl H H Cl H CH₂ 7.199 cyclopropyl Cl H H H H O 7.200cyclopropyl Cl H H Me H O 7.201 cyclopropyl Cl H H F H O 7.202cyclopropyl Cl H H Cl H O 7.203 Me Me F H H H H CH₂ white solid 7.204 MeMe F H H Me H CH₂ 7.205 Me Me F H H F H CH₂ 7.206 Me Me F H H Cl H CH₂7.207 Me Me F Me H Me H CH₂ 7.208 Me Me F H Me Me H CH₂ 7.209 Me Me F HH Me Me CH₂ 7.210 Me Me F H F Me H CH₂ 7.211 Me Me F H Cl Cl H CH₂ 7.212Me Me F H H H H O 7.213 Me Me F H H Me H O 7.214 Me Me F H H F H O 7.215Me Me F H H Cl H O 7.216 Me Me Cl H H H H direct bond 7.217 Me Me Cl H HMe H direct bond 7.218 Me Me Cl H H F H direct bond 7.219 Me Me Cl H HCl H direct bond 7.220 Me Me Cl H H H H CH₂ 7.221 Me Me Cl H H Me H CH₂7.222 Me Me Cl H H F H CH₂ 7.223 Me Me Cl H H Cl H CH₂ 7.224 Me Me Cl HH H H O 7.225 Me Me Cl H H Me H O 7.226 Me Me Cl H H F H O 7.227 Me MeCl H H Cl H O 7.228 Me Me F H H H H direct bond white solid 7.229 Me MeF H H Me H direct bond white solid 7.230 Me Me F H H F H direct bond7.231 Me Me F H H Cl H direct bond 7.232 Me Me F H H Br H direct bond7.233 Me Me F Me H Me H direct bond 7.234 Me Me F H Me Me H direct bond7.235 Me Me F H H Me Me direct bond 7.236 Me Me F H F Me H direct bond7.237 Me Me F H Cl Cl H direct bond 7.238 CH₂—SCF₃ H H H Me H directbond waxy 7.239 F F F H H H H direct bond solid 7.240 F F F H H Me Hdirect bond solid 7.241 CH₂—SCF₃ H H H H H H direct bond solid 7.242 CNH H H H H H direct bond white solid 7.243 CN F H H H Me H direct bondsolid 7.244 F F H H H H H direct bond solid 7.245 Pr H H H H Me H directbond white solid Notes to physical data in Table 7 (reference is made tothe compound no. in Table 7): Cpd. 7.1: mp 163.5° C.; Cpd. 7.2: mp90-92° C., optical rotation +179.4°; Cpd. 7.72: mp 58-60° C.; Cpd.7.203: optical rotation +83.4° Cpd. 7.239: mp 180-183 ° C., opticalrotation +153.4°; Cpd. 7.240: mp. 80-83° C.; Cpd. 7.241: mp 50-52° C.,optical rotation +109.6°; Cpd. 7.242: optical rotation +116.2°; Cpd.7.243: mp 64-66° C., optical rotation +135.0°; Cpd. 7.244: mp 72-76° C.

TABLE 8 Compounds of formula (Ik): (Ik)

  [In the compounds of formula (Ij-1) the carbon atom marked *1 isachiral] Physical Cpd R¹ R² R³ R⁷ R⁸ R⁹ R¹⁰ A data 8.1 H H H H H H Hdirect bond white solid 8.2 H H H H H Me H direct bond white solid 8.3 HH H H H F H direct bond solid 8.4 H H H H H Cl H direct bond 8.5 H H H HH Br H direct bond 8.6 H H H Me H Me H direct bond 8.7 H H H H Me Me Hdirect bond wax 8.8 H H H H H Me Me direct bond 8.9 H H H H F Me Hdirect bond 8.10 H H H H Cl Cl H direct bond 8.11 H H H H H H H CH₂white foam 8.12 H H H H H Me H CH₂ solid 8.13 H H H H H F H CH₂ 8.14 H HH H H Cl H CH₂ 8.15 H H H Me H Me H CH₂ solid 8.16 H H H H Me Me H CH₂8.17 H H H H H Me Me CH₂ 8.18 H H H H F Me H CH₂ 8.19 H H H H Cl Cl HCH₂ 8.20 H H H H H H H O 8.21 H H H H H Me H O solid 8.22 H H H H H F HO 8.23 H H H H H Cl H O 8.24 Me H H H H H H direct bond solid 8.25 Me HH H H Me H direct bond yellow syrup 8.26 Me H H H H F H direct bondsolid 8.27 Me H H H H Cl H direct bond 8.28 Me H H H H Br H direct bond8.29 Me H H Me H Me H direct bond 8.30 Me H H H Me Me H direct bond 8.31Me H H H H Me Me direct bond 8.32 Me H H H F Me H direct bond 8.33 Me HH H Cl Cl H direct bond 8.34 Me H H H H H H CH₂ solid foam 8.35 Me H H HH Me H CH₂ solid 8.36 Me H H H H F H CH₂ 8.37 Me H H H H Cl H CH₂ 8.38Me H H Me H Me H CH₂ solid 8.39 Me H H H Me Me H CH₂ 8.40 Me H H H H MeMe CH₂ 8.41 Me H H H F Me H CH₂ 8.42 Me H H H Cl Cl H CH₂ 8.43 Me H H HH H H O 8.44 Me H H H H Me H O solid 8.45 Me H H H H F H O 8.46 Me H H HH Cl H O 8.47 Et H H H H H H direct bond 8.48 Et H H H H Me H directbond colour- less foam 8.49 Et H H H H F H direct bond solid 8.50 Et H HH H Cl H direct bond 8.51 Et H H H H Br H direct bond 8.52 Et H H Me HMe H direct bond 8.53 Et H H H Me Me H direct bond 8.54 Et H H H H Me Medirect bond 8.55 Et H H H F Me H direct bond 8.56 Et H H H Cl Cl Hdirect bond 8.57 Et H H H H H H CH₂ 8.58 Et H H H H Me H CH₂ solid 8.59Et H H H H F H CH₂ 8.60 Et H H H H Cl H CH₂ 8.61 Et H H Me H Me H CH₂solid 8.62 Et H H H Me Me H CH₂ 8.63 Et H H H H Me Me CH₂ 8.64 Et H H HF Me H CH₂ 8.65 Me Me Cl H H Cl H O 8.66 Me Me H H H H H direct bond8.67 Me Me H H H Me H direct bond white solid 8.68 Me Me H H H F Hdirect bond solid 8.69 Me Me H H H Cl H direct bond 8.70 Me Me H H H H HCH₂ 8.71 Me Me H H H Me H CH₂ solid 8.72 Me Me H H H F H CH₂ 8.73 Me MeH H H Cl H CH₂ 8.74 Me Me H H H H H O 8.75 Me Me H H H Me H O solid 8.76Me Me H H H F H O 8.77 Me Me H H H Cl H O 8.78 Cl Me Cl H H H H directbond 8.79 Cl Me Cl H H Me H direct bond colour- less solid 8.80 Cl Me ClH H F H direct bond 8.81 Cl Me Cl H H Cl H direct bond 8.82 Cl Me Cl H HH H CH₂ 8.83 Cl Me Cl H H Me H CH₂ 8.84 Cl Me Cl H H F H CH₂ 8.85 Cl MeCl H H Cl H CH₂ 8.86 Cl Me Cl H H H H O 8.87 Cl Me Cl H H Me H O 8.88 ClMe Cl H H F H O 8.89 Cl Me Cl H H Cl H O 8.90 H H F H H H H direct bondsolid 8.91 H H F H H Me H direct bond 8.92 H H F H H F H direct bond8.93 H H F H H Cl H direct bond 8.94 H H F H H Br H direct bond 8.95 H HF Me H Me H direct bond 8.96 H H F H Me Me H direct bond 8.97 H H F H HMe Me direct bond 8.98 H H F H F Me H direct bond 8.99 H H F H Cl Cl Hdirect bond 8.100 H H F H H H H CH₂ solid 8.101 H H F H H Me H CH₂ 8.102H H F H H F H CH₂ 8.103 H H F H H Cl H CH₂ 8.104 H H F Me H Me H CH₂8.105 H H F H Me Me H CH₂ 8.106 H H F H H Me Me CH₂ 8.107 H H F H F Me HCH₂ 8.108 H H F H Cl Cl H CH₂ 8.109 H H F H H H H O 8.110 H H F H H Me HO 8.111 H H F H H F H O 8.112 H H F H H Cl H O 8.113 H H Cl H H H Hdirect bond solid 8.114 H H Cl H H Me H direct bond 8.115 H H Cl H H F Hdirect bond 8.116 H H Cl H H Cl H direct bond 8.117 H H Cl H H H H CH₂waxy 8.118 H H Cl H H Me H CH₂ 8.119 H H Cl H H F H CH₂ 8.120 H H Cl H HCl H CH₂ 8.121 H H Cl H H H H O 8.122 H H Cl H H Me H O 8.123 H H Cl H HF H O 8.124 H H Cl H H Cl H O 8.125 cyclopropyl H H H H H direct bond8.126 cyclopropyl H H H Me H direct bond 8.127 cyclopropyl H H H F Hdirect bond 8.128 cyclopropyl H H H Cl H direct bond 8.129 cyclopropyl HH H Br H direct bond 8.130 cyclopropyl H Me H Me H direct bond 8.131cyclopropyl H H Me Me H direct bond 8.132 cyclopropyl H H H Me Me directbond 8.133 cyclopropyl H H F Me H direct bond 8.134 cyclopropyl H H ClCl H direct bond 8.135 cyclopropyl H H H H H CH₂ 8.136 cyclopropyl H H HMe H CH₂ 8.137 cyclopropyl H H H F H CH₂ 8.138 cyclopropyl H H H Cl HCH₂ 8.139 cyclopropyl H Me H Me H CH₂ 8.140 cyclopropyl H H Me Me H CH₂8.141 cyclopropyl H H H Me Me CH₂ 8.142 cyclopropyl H H F Me H CH₂ 8.143cyclopropyl H H Cl Cl H CH₂ 8.144 cyclopropyl H H H H H O 8.145cyclopropyl H H H Me H O 8.146 cyclopropyl H H H F H O 8.147 cyclopropylH H H Cl H O 8.148 cyclopropyl Me H H H H direct bond waxy 8.149cyclopropyl Me H H Me H direct bond 8.150 cyclopropyl Me H H F H directbond 8.151 cyclopropyl Me H H Cl H direct bond 8.152 cyclopropyl Me H HH H CH₂ wax 8.153 cyclopropyl Me H H Me H CH₂ 8.154 cyclopropyl Me H H FH CH₂ 8.155 cyclopropyl Me H H Cl H CH₂ 8.156 cyclopropyl Me H H H H O8.157 cyclopropyl Me H H Me H O 8.158 cyclopropyl Me H H F H O 8.159cyclopropyl Me H H Cl H O 8.160 cyclopropyl F H H H H direct bond solid8.161 cyclopropyl F H H Me H direct bond 8.162 cyclopropyl F H H F Hdirect bond 8.163 cyclopropyl F H H Cl H direct bond 8.164 cyclopropyl FH H Br H direct bond 8.165 cyclopropyl F Me H Me H direct bond 8.166cyclopropyl F H Me Me H direct bond 8.167 cyclopropyl F H H Me Me directbond 8.168 cyclopropyl F H F Me H direct bond 8.169 cyclopropyl F H ClCl H direct bond 8.170 cyclopropyl F H H H H CH₂ solid 8.171 cyclopropylF H H Me H CH₂ 8.172 cyclopropyl F H H F H CH₂ 8.173 cyclopropyl F H HCl H CH₂ 8.174 cyclopropyl F Me H Me H CH₂ 8.175 cyclopropyl F H Me Me HCH₂ 8.176 cyclopropyl F H H Me Me CH₂ 8.177 cyclopropyl F H F Me H CH₂8.178 cyclopropyl F H Cl Cl H CH₂ 8.179 cyclopropyl F H H H H O 8.180cyclopropyl F H H Me H O 8.181 cyclopropyl F H H F H O 8.182 cyclopropylF H H Cl H O 8.183 cyclopropyl Cl H H H H direct bond solid 8.184cyclopropyl Cl H H Me H direct bond 8.185 cyclopropyl Cl H H F H directbond 8.186 cyclopropyl Cl H H Cl H direct bond 8.187 cyclopropyl Cl H HH H CH₂ solid 8.188 cyclopropyl Cl H H Me H CH₂ 8.189 cyclopropyl Cl H HF H CH₂ 8.190 cyclopropyl Cl H H Cl H CH₂ 8.191 cyclopropyl Cl H H H H O8.192 cyclopropyl Cl H H Me H O 8.193 cyclopropyl Cl H H F H O 8.194cyclopropyl Cl H H Cl H O 8.195 Me Me F H H H H direct bond solid 8.196Me Me F H H Me H direct bond light brown solid 8.197 Me Me F H H F Hdirect bond solid 8.198 Me Me F H H Cl H direct bond 8.199 Me Me F H HBr H direct bond 8.200 Me Me F Me H Me H direct bond 8.201 Me Me F H MeMe H direct bond solid foam 8.202 Me Me F H H Me Me direct bond 8.203 MeMe F H F Me H direct bond 8.204 Me Me F H Cl Cl H direct bond 8.205 MeMe F H H H H CH₂ beige solid 8.206 Me Me F H H Me H CH₂ solid 8.207 MeMe F H H F H CH₂ 8.208 Me Me F H H Cl H CH₂ 8.209 Me Me F Me H Me H CH₂solid 8.210 Me Me F H Me Me H CH₂ 8.211 Me Me F H H Me Me CH₂ 8.212 MeMe F H F Me H CH₂ 8.213 Me Me F H Cl Cl H CH₂ 8.214 Me Me F H H H H O8.215 Me Me F H H Me H O solid 8.216 Me Me F H H F H O 8.217 Me Me F H HCl H O 8.218 Me Me Cl H H H H direct bond 8.219 Me Me Cl H H Me H directbond color- less solid 8.220 Me Me Cl H H F H direct bond 8.221 Me Me ClH H Cl H direct bond 8.222 Me Me Cl H H H H CH₂ 8.223 Me Me Cl H H Me HCH₂ 8.224 Me Me Cl H H F H CH₂ 8.225 Me Me Cl H H Cl H CH₂ 8.226 Me MeCl H H H H O 8.227 Me Me Cl H H Me H O 8.228 Me Me Cl H H F H O 8.229 EtH H H Cl Cl H CH₂ 8.230 Et H H H H H H O 8.231 Et H H H H Me H O solid8.232 Et H H H H F H O 8.233 OMe H H H H H H direct bond solid 8.234 OMeH H H H H H CH₂ solid 8.235 OMe H H H H Me H direct bond 8.236 OMe H H HH Me H CH₂ 8.237 Me Me F F H H H O solid 8.238 H H H F H H H O whitesolid 8.239 Me H H F H H H O white solid 8.240 Et H H F H H H O solid8.241 Me Me F Me Me H H O waxy 8.242 Me H H Me Me H H O waxy 8.243 Me MeF H H OMe H direct bond waxy 8.244 Me H H H H OMe H direct bond waxy8.245 Me Me F H H Et H direct bond solid 8.246 H H H H H Et H directbond solid 8.247 Me Me H H H Et H direct bond solid 8.248 Me H H H H EtH direct bond solid 8.249 Et H H H H Et H direct bond solid 8.250CH₂—SCF₃ H H H H Et H direct bond waxy 8.251 CH₂—SCF₃ H H H H Me H CH₂waxy 8.252 Me Me H Me H Me H CH₂ solid 8.253 OMe H H Me H Me H CH₂ whitesolid 8.254 F F F H H H H CH₂ solid 8.255 CN H H H H H H CH₂ white solid8.256 F F H H H H H CH₂ solid 8.257 Pr H H H H Et H CH₂ solid Notes tophysical data in Table 8 (reference is made to the compound no. in Table8): Cpd. 8.1: mp 94-96° C., optical rotation +87.4°; Cpd. 8.2: mp100-102° C.; Cpd. 8.3: mp 87-89° C., optical rotation +97.2°; Cpd. 8.11:optical rotation +78.7°; Cpd. 8.12: mp 95-98° C., optical rotation+73.5°; Cpd. 8.15: mp 100-103° C., optical rotation +92.1°; Cpd. 8.21:mp 95-97° C., optical rotation +44.3°; Cpd. 8.24: mp 65-70° C., opticalrotation +95.7°; Cpd. 8.26: mp 77-78° C., optical rotation +80.0°; Cpd.8.34: optical rotation +98.5°; Cpd. 8.35: mp 77-80° C., optical rotation+79.3°; Cpd. 8.38: mp 172-174° C.; Cpd. 8.44: mp 75-79° C., opticalrotation +56.3°; Cpd. 8.49: mp 138-139° C., optical rotation +122.1°;Cpd. 8.58: mp 135-138° C., optical rotation +69.0°; Cpd. 8.61: mp178-180° C.; Cpd. 8.67: mp 83-84° C.; Cpd. 8.68: mp 67-68° C., opticalrotation +74.2°; Cpd. 8.71: mp 73-75° C., optical rotation +77.7°; Cpd.8.75: mp 75-78° C., optical rotation +59.4°; Cpd. 8.79: mp 149-151° C.;Cpd. 8.90: mp 163-165° C., optical rotation +91.6°; Cpd. 8.100: mp114-117° C., optical rotation +94.1°; Cpd. 8.113: mp 63-68° C., opticalrotation +77.6°; Cpd. 8.117; optical rotation +64.0°; Cpd. 8.152:optical rotation +75.3°; Cpd. 8.160: mp 70-75° C., optical rotation+75.0°; Cpd. 8.195: mp 125-126° C., optical rotation +87.7°; Cpd. 8.196:mp 87-89° C. Cpd. 8.197: mp 87-89° C., optical rotation +68.8°; Cpd.8.205: mp 165-167° C.; Cpd. 8.206: mp 87-90° C., optical rotation+60.5°; Cpd. 8.209: mp 90-93° C.; Cpd. 8.215: mp 100-108° C., opticalrotation +42.0°; Cpd. 8.219: mp 136-138° C.; Cpd. 8.231: mp 70-75° C.,optical rotation +49.3°; Cpd. 8.233: mp 148-155° C., optical rotation+86.9°; Cpd. 8.234: mp 135-140° C., optical rotation +81.8°; Cpd. 8.237:mp 87-95° C., optical rotation +68.0°; Cpd. 8.239: optical rotation+52.7°; Cpd. 8.240: mp 87-88° C., optical rotation +55.5°; Cpd. 8.243:optical rotation +63.0°; Cpd. 8.245: mp 136-139° C., optical rotation+66.7°; Cpd. 8.246: mp 73-75° C., optical rotation +75.0°; Cpd. 8.247:mp 63-70° C., optical rotation +75.0°; Cpd. 8.248: mp 63-70° C., opticalrotation +71.2°; Cpd. 8.252: mp 70-75° C.; Cpd. 8.254: mp 170-173° C.,optical rotation +109.6°; Cpd. 8.256: mp 72-76° C. Cpd. 8.257: mp 63-65°C.

In the following Tables 9 to 14 where the stereochemistry of one or morechiral centres is specified, it is understood that the optical purity atthe 1R position is at least 90% in the Table examples.

TABLE 9 Compounds of formula (IL) wherein the stereochemicalconfiguration at the carbon atom marked 1* is chiral but racemic i.e.(1* R,S): (IL)

Cpd R¹ R² R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A Physical data 9.1  Me H F Me H H H Hdirect bond 9.2  Me H F Me H H Me H direct bond 9.3  Me H F Me H H F Hdirect bond 9.4  Me H F Me H H Cl H direct bond 9.5  Me H F Me H H Br Hdirect bond 9.6  Me H F Me Me H Me H direct bond 9.7  Me H F Me H Me MeH direct bond 9.8  Me H F Me H H Me Me direct bond 9.9  Me H F Me H F MeH direct bond 9.10 Me H F Me H Cl Cl H direct bond 9.11 Me H F Me H H HH CH₂ 9.12 Me H F Me H H Me H CH₂ 9.13 Me H F Me H H F H CH₂ 9.14 Me H FMe H H Cl H CH₂ 9.15 Me H F Me Me H Me H CH₂ 9.16 Me H F Me H Me Me HCH₂ 9.17 Me H F Me H H Me Me CH₂ 9.18 Me H F Me H F Me H CH₂ 9.19 Me H FMe H Cl Cl H CH₂ 9.20 Me H F Me H H H H O 9.21 Me H F Me H H Me H O 9.22Me H F Me H H F H O 9.23 Me H F Me H H Cl H O 9.24 Me H Cl Me H H H Hdirect bond 9.25 Me H Cl Me H H Me H direct bond 9.26 Me H Cl Me H H F Hdirect bond 9.27 Me H Cl Me H H Cl H direct bond 9.28 Me H Cl Me H H H HCH₂ 9.29 Me H Cl Me H H Me H CH₂ 9.30 Me H Cl Me H H F H CH₂ 9.31 Me HCl Me H H Cl H CH₂ 9.32 Me H Cl Me H H H H O 9.33 Me H Cl Me H H Me H O9.34 Me H Cl Me H H F H O 9.35 Me H Cl Me H H Cl H O 9.36 Et H F Me H HH H direct bond white solid 9.37 Et H F Me H H Me H direct bond whitesolid 9.38 Et H F Me H H F H direct bond 9.39 Et H F Me H H Cl H directbond 9.40 Et H F Me H H Br H direct bond 9.41 Et H Cl Me H H H H directbond 9.42 Et H Cl Me H H Me H direct bond 9.43 Et H Cl Me H H F H directbond 9.44 Et H Cl Me H H Cl H direct bond 9.45 Et H Cl Me H H Br Hdirect bond 9.46 Et H F Me H H H H CH₂ 9.47 Et H F Me H H Me H CH₂ 9.48Et H F Me H H F H CH₂ 9.49 Et H F Me H H Cl H CH₂ 9.50 Et H F Me H H BrH CH₂ 9.51 Et H Cl Me H H H H CH₂ 9.52 Et H Cl Me H H Me H CH₂ 9.53 Et HCl Me H H F H CH₂ 9.54 Et H Cl Me H H Cl H CH₂ 9.55 Et H Cl Me H H Br HCH₂ 9.56 Et H F Me H H H H O 9.57 Et H F Me H H Me H O 9.58 Et H F Me HH F H O 9.59 Et H F Me H H Cl H O 9.60 Et H F Me H H Br H O 9.61 Et H ClMe H H H H O 9.62 Et H Cl Me H H Me H O 9.63 Et H Cl Me H H F H O 9.64Et H Cl Me H H Cl H O 9.65 Et H Cl Me H H Br H O 9.66 Pr H H Me H H Me Hdirect bond white solid

TABLE 10 Compounds of formula (Ia-1) which have a chiral centre at thecarbon atom marked 1*, wherein the stereochemical configuration at thecarbon atom marked 1* is racemic i.e. (1*RS): (Ia-1)

Cpd R¹ R² R³ R⁷ R⁸ R⁹ R¹⁰ A Physical data 10.1  Me H F H H H H directbond white solid 10.2  Me H F H H Me H direct bond white solid 10.3  MeH F H H F H direct bond 10.4  Me H F H H Cl H direct bond 10.5  Me H F HH Br H direct bond 10.6  Me H F Me H Me H direct bond 10.7  Me H F H MeMe H direct bond 10.8  Me H F H H Me Me direct bond 10.9  Me H F H F MeH direct bond 10.10 Me H F H Cl Cl H direct bond 10.11 Me H F H H H HCH₂ 10.12 Me H F H H Me H CH₂ 10.13 Me H F H H F H CH₂ 10.14 Me H F H HCl H CH₂ 10.15 Me H F Me H Me H CH₂ 10.16 Me H F H Me Me H CH₂ 10.17 MeH F H H Me Me CH₂ 10.18 Me H F H F Me H CH₂ 10.19 Me H F H Cl Cl H CH₂10.20 Me H F H H H H O 10.21 Me H F H H Me H O 10.22 Me H F H H F H O10.23 Me H F H H Cl H O 10.24 Me H Cl H H H H direct bond 10.25 Me H ClH H Me H direct bond 10.26 Me H Cl H H F H direct bond 10.27 Me H Cl H HCl H direct bond 10.28 Me H Cl H H H H CH₂ 10.29 Me H Cl H H Me H CH₂10.30 Me H Cl H H F H CH₂ 10.31 Me H Cl Me H Me H CH₂ 10.32 Me H Cl H HH H O 10.33 Me H Cl H H Me H O 10.34 Me H Cl H H F H O 10.35 Me H Cl H HCl H O 10.36 Et H F H H H H direct bond 10.37 Et H F H H Me H directbond white solid (c) 10.38 Et H F H H F H direct bond solid 10.39 Et H FH H Cl H direct bond 10.40 Et H F H H Br H direct bond 10.41 Et H Cl H HH H direct bond 10.42 Et H Cl H H Me H direct bond 10.43 Et H Cl H H F Hdirect bond 10.44 Et H Cl H H Cl H direct bond 10.45 Et H Cl H H Br Hdirect bond 10.46 Et H F H H H H CH₂ 10.47 Et H F H H Me H CH₂ solid10.48 Et H F H H F H CH₂ 10.49 Et H F H H Cl H CH₂ 10.50 Et H F H H Br HCH₂ 10.51 Et H Cl H H H H CH₂ 10.52 Et H Cl H H Me H CH₂ 10.53 Et H Cl HH F H CH₂ 10.54 Et H Cl H H Cl H CH₂ 10.55 Et H Cl H H Br H CH₂ 10.56 EtH F H H H H O 10.57 Et H F H H Me H O solid 10.58 Et H F H H F H O 10.59Et H F H H Cl H O 10.60 Et H F H H Br H O 10.61 Et H Cl H H H H O 10.62Et H Cl H H Me H O 10.63 Et H Cl H H F H O 10.64 Et H Cl H H Cl H O10.65 Et H Cl H H Br H O 10.66 Pr H F H H Me H CH₂ white solid 10.67 PrH F Me H Me H O solid 10.68 ET H F Me H Me H CH₂ solid Notes to physicaldata in Table 10 (reference is made to the compound no. in Table 10):Cpd 10.1: mp 147-151° C., optical rotation +91.5°; Cpd 10.2: mp 92-94°C.; Cpd 10.37: mp 82-84° C. Cpd 10.38: mp 76-77° C.; Cpd 10.47: mp85-88° C.; Cpd 10.57: mp 90-93° C.; Cpd 10.67: mp 80-85° C.; Cpd 10.68:mp 90-93° C., optical rotation +77.0

TABLE 11 Compounds of formula (Im) wherein the stereochemicalconfiguration at the carbon atom marked 1* is racemic i.e. (1*RS): (Im)

Physical data mp/opt. rot./ Cpd R¹ R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A appearance 11.1 Me F Me H H H H direct bond 11.2  Me F Me H H Me H direct bond 11.3  MeF Me H H F H direct bond 11.4  Me F Me H H Cl H direct bond 11.5  Me FMe H H Br H direct bond 11.6  Me F Me Me H Me H direct bond 11.7  Me FMe H Me Me H direct bond 11.8  Me F Me H H Me Me direct bond 11.9  Me FMe H F Me H direct bond 11.10 Me F Me H Cl Cl H direct bond 11.11 Me FMe H H H H CH₂ 11.12 Me F Me H H Me H CH₂ 11.13 Me F Me H H F H CH₂11.14 Me F Me H H Cl H CH₂ 11.15 Me F Me Me H Me H CH₂ 11.16 Me F Me HMe Me H CH₂ 11.17 Me F Me H H Me Me CH₂ 11.18 Me F Me H F Me H CH₂ 11.19Me F Me H Cl Cl H CH₂ 11.20 Me F Me H H H H O 11.21 Me F Me H H Me H O11.22 Me F Me H H F H O 11.23 Me F Me H H Cl H O 11.24 Me Cl Me H H H Hdirect bond 11.25 Me Cl Me H H Me H direct bond 11.26 Me Cl Me H H F Hdirect bond 11.27 Me Cl Me H H Cl H direct bond 11.28 Me Cl Me H H H HCH₂ 11.29 Me Cl Me H H Me H CH₂ 11.30 Me Cl Me H H F H CH₂ 11.31 Me ClMe H H Cl H CH₂ 11.32 Me Cl Me H H H H O 11.33 Me Cl Me H H Me H O 11.34Me Cl Me H H F H O 11.35 Me Cl Me H H Cl H O 11.36 Et F Me H H H Hdirect bond 11.37 Et F Me H H Me H direct bond 11.38 Et F Me H H F Hdirect bond 11.39 Et F Me H H Cl H direct bond 11.40 Et F Me H H Br Hdirect bond 11.41 Et Cl Me H H H H direct bond 11.42 Et Cl Me H H Me Hdirect bond 11.43 Et Cl Me H H F H direct bond 11.44 Et Cl Me H H Cl Hdirect bond 11.45 Et Cl Me H H Br H direct bond 11.46 Et F Me H H H HCH₂ 11.47 Et F Me H H Me H CH₂ 11.48 Et F Me H H F H CH₂ 11.49 Et F Me HH Cl H CH₂ 11.50 Et F Me H H Br H CH₂ 11.51 Et Cl Me H H H H CH₂ 11.52Et Cl Me H H Me H CH₂ 11.53 Et Cl Me H H F H CH₂ 11.54 Et Cl Me H H Cl HCH₂ 11.55 Et Cl Me H H Br H CH₂ 11.56 Et F Me H H H H O 11.57 Et F Me HH Me H O 11.58 Et F Me H H F H O 11.59 Et F Me H H Cl H O 11.60 Et F MeH H Br H O 11.61 Et Cl Me H H H H O 11.62 Et Cl Me H H Me H O 11.63 EtCl Me H H F H O 11.64 Et Cl Me H H Cl H O 11.65 Et Cl Me H H Br H O

TABLE 12 Compounds of formula (In) wherein the stereochemicalconfiguration at the carbon atom marked 2 is racemic i.e. (2RS): (In)

Physical data mp/opt. rot./ Cpd R¹ R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A appearance 12.1Me F Me H H H H direct bond 12.2 Me F Me H H Me H direct bond 12.3 Me FMe H H F H direct bond 12.4 Me F Me H H Cl H direct bond 12.5 Me F Me HH Br H direct bond 12.6 Me F Me Me H Me H direct bond 12.7 Me F Me H MeMe H direct bond 12.8 Me F Me H H Me Me direct bond 12.9 Me F Me H F MeH direct bond 12.10 Me F Me H Cl Cl H direct bond 12.11 Me F Me H H H HCH₂ 12.12 Me F Me H H Me H CH₂ 12.13 Me F Me H H F H CH₂ 12.14 Me F Me HH Cl H CH₂ 12.15 Me F Me Me H Me H CH₂ 12.16 Me F Me H Me Me H CH₂ 12.17Me F Me H H Me Me CH₂ 12.18 Me F Me H F Me H CH₂ 12.19 Me F Me H Cl Cl HCH₂ 12.20 Me F Me H H H H O 12.21 Me F Me H H Me H O 12.22 Me F Me H H FH O 12.23 Me F Me H H Cl H O 12.24 Me Cl Me H H H H direct bond 12.25 MeCl Me H H Me H direct bond 12.26 Me Cl Me H H F H direct bond 12.27 MeCl Me H H Cl H direct bond 12.28 Me Cl Me H H H H CH₂ 12.29 Me Cl Me H HMe H CH₂ 12.30 Me Cl Me H H F H CH₂ 12.31 Me Cl Me H H Cl H CH₂ 12.32 MeCl Me H H H H O 12.33 Me Cl Me H H Me H O 12.34 Me Cl Me H H F H O 12.35Me Cl Me H H Cl H O 12.36 Et F Me H H H H direct bond 12.37 Et F Me H HMe H direct bond 12.38 Et F Me H H F H direct bond 12.39 Et F Me H H ClH direct bond 12.40 Et F Me H H Br H direct bond 12.41 Et Cl Me H H H Hdirect bond 12.42 Et Cl Me H H Me H direct bond 12.43 Et Cl Me H H F Hdirect bond 12.44 Et Cl Me H H Cl H direct bond 12.45 Et Cl Me H H Br Hdirect bond 12.46 Et F Me H H H H CH₂ 12.47 Et F Me H H Me H CH₂ 12.48Et F Me H H F H CH₂ 12.49 Et F Me H H Cl H CH₂ 12.50 Et F Me H H Br HCH₂ 12.51 Et Cl Me H H H H CH₂ 12.52 Et Cl Me H H Me H CH₂ 12.53 Et ClMe H H F H CH₂ 12.54 Et Cl Me H H Cl H CH₂ 12.55 Et Cl Me H H Br H CH₂12.56 Et F Me H H H H O 12.57 Et F Me H H Me H O 12.58 Et F Me H H F H O12.59 Et F Me H H Cl H O 12.60 Et F Me H H Br H O 12.61 Et Cl Me H H H HO 12.62 Et Cl Me H H Me H O 12.63 Et Cl Me H H F H O 12.64 Et Cl Me H HCl H O 12.65 Et Cl Me H H Br H O

TABLE 13 Compounds of formula (Ip) wherein the stereochemicalconfiguration at the carbon atom marked 2 is racemic i.e. (2RS): (Ip)

Physical data mp/opt. rot./ Cpd R¹ R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A appearance 13.1Me F Me H H H H direct bond 13.2 Me F Me H H Me H direct bond 13.3 Me FMe H H F H direct bond 13.4 Me F Me H H Cl H direct bond 13.5 Me F Me HH Br H direct bond 13.6 Me F Me Me H Me H direct bond 13.7 Me F Me H MeMe H direct bond 13.8 Me F Me H H Me Me direct bond 13.9 Me F Me H F MeH direct bond 13.10 Me F Me H Cl Cl H direct bond 13.11 Me F Me H H H HCH₂ 13.12 Me F Me H H Me H CH₂ 12.13 Me F Me H H F H CH₂ 13.14 Me F Me HH Cl H CH₂ 13.15 Me F Me Me H Me H CH₂ 13.16 Me F Me H Me Me H CH₂ 13.17Me F Me H H Me Me CH₂ 13.18 Me F Me H F Me H CH₂ 13.19 Me F Me H Cl Cl HCH₂ 13.20 Me F Me H H H H O 13.21 Me F Me H H Me H O 13.22 Me F Me H H FH O 13.23 Me F Me H H Cl H O 13.24 Me Cl Me H H H H direct bond 13.25 MeCl Me H H Me H direct bond 13.26 Me Cl Me H H F H direct bond 13.27 MeCl Me H H Cl H direct bond 13.28 Me Cl Me H H H H CH₂ 13.29 Me Cl Me H HMe H CH₂ 13.30 Me Cl Me H H F H CH₂ 13.31 Me Cl Me H H Cl H CH₂ 13.32 MeCl Me H H H H O 13.33 Me Cl Me H H Me H O 13.34 Me Cl Me H H F H O 13.35Me Cl Me H H Cl H O 13.36 Et F Me H H H H direct bond 13.37 Et F Me H HMe H direct bond 13.38 Et F Me H H F H direct bond 13.39 Et F Me H H ClH direct bond 13.40 Et F Me H H Br H direct bond 13.41 Et Cl Me H H H Hdirect bond 13.42 Et Cl Me H H Me H direct bond 13.43 Et Cl Me H H F Hdirect bond 13.44 Et Cl Me H H Cl H direct bond 13.45 Et Cl Me H H Br Hdirect bond 13.46 Et F Me H H H H CH₂ 13.47 Et F Me H H Me H CH₂ 13.48Et F Me H H F H CH₂ 13.49 Et F Me H H Cl H CH₂ 13.50 Et F Me H H Br HCH₂ 13.51 Et Cl Me H H H H CH₂ 13.52 Et Cl Me H H Me H CH₂ 13.53 Et ClMe H H F H CH₂ 13.54 Et Cl Me H H Cl H CH₂ 13.55 Et Cl Me H H Br H CH₂13.56 Et F Me H H H H O 13.57 Et F Me H H Me H O 13.58 Et F Me H H F H O13.59 Et F Me H H Cl H O 13.60 Et F Me H H Br H O 13.61 Et Cl Me H H H HO 13.62 Et Cl Me H H Me H O 13.63 Et Cl Me H H F H O 13.64 Et Cl Me H HCl H O 13.65 Et Cl Me H H Br H O

TABLE 14 Compounds of formula (Ic-1) wherein the stereochemicalconfigurations at the carbon atoms marked 2 and 1* are racemic i.e.(1*RS, 2RS): (Ic-1)

Physical data mp/opt. rot./ Cpd R¹ R³ R⁶ R⁷ R⁸ R⁹ R¹⁰ A appearance 14.1Me F Me H H H H direct bond 14.2 Me F Me H H Me H direct bond 14.3 Me FMe H H F H direct bond 14.4 Me F Me H H Cl H direct bond 14.5 Me F Me HH Br H direct bond 14.6 Me F Me Me H Me H direct bond 14.7 Me F Me H MeMe H direct bond 14.8 Me F Me H H Me Me direct bond 14.9 Me F Me H F MeH direct bond 14.10 Me F Me H Cl Cl H direct bond 14.11 Me F Me H H H HCH₂ 14.12 Me F Me H H Me H CH₂ 14.13 Me F Me H H F H CH₂ 14.14 Me F Me HH Cl H CH₂ 14.15 Me F Me Me H Me H CH₂ 14.16 Me F Me H Me Me H CH₂ 14.17Me F Me H H Me Me CH₂ 14.18 Me F Me H F Me H CH₂ 14.19 Me F Me H Cl Cl HCH₂ 14.20 Me F Me H H H H O 14.21 Me F Me H H Me H O 14.22 Me F Me H H FH O 14.23 Me F Me H H Cl H O 14.24 Me Cl Me H H H H direct bond 14.25 MeCl Me H H Me H direct bond 14.26 Me Cl Me H H F H direct bond 14.27 MeCl Me H H Cl H direct bond 14.28 Me Cl Me H H H H CH₂ 14.29 Me Cl Me H HMe H CH₂ 14.30 Me Cl Me H H F H CH₂ 14.31 Me Cl Me H H Cl H CH₂ 14.32 MeCl Me H H H H O 14.33 Me Cl Me H H Me H O 14.34 Me Cl Me H H F H O 14.35Me Cl Me H H Cl H O 14.36 Et F Me H H H H direct bond 14.37 Et F Me H HMe H direct bond 14.38 Et F Me H H F H direct bond 14.39 Et F Me H H ClH direct bond 14.40 Et F Me H H Br H direct bond 14.41 Et Cl Me H H H Hdirect bond 14.42 Et Cl Me H H Me H direct bond 14.43 Et Cl Me H H F Hdirect bond 14.44 Et Cl Me H H Cl H direct bond 14.45 Et Cl Me H H Br Hdirect bond 14.46 Et F Me H H H H CH₂ 14.47 Et F Me H H Me H CH₂ 14.48Et F Me H H F H CH₂ 14.49 Et F Me H H Cl H CH₂ 14.50 Et F Me H H Br HCH₂ 14.51 Et Cl Me H H H H CH₂ 14.52 Et Cl Me H H Me H CH₂ 14.53 Et ClMe H H F H CH₂ 14.54 Et Cl Me H H Cl H CH₂ 14.55 Et Cl Me H H Br H CH₂14.56 Et F Me H H H H O 14.57 Et F Me H H Me H O 14.58 Et F Me H H F H O14.59 Et F Me H H Cl H O 14.60 Et F Me H H Br H O 14.61 Et Cl Me H H H HO 14.62 Et Cl Me H H Me H O 14.63 Et Cl Me H H F H O 14.64 Et Cl Me H HCl H O 14.65 Et Cl Me H H Br H O

The following Table 15 illustrates the intermediate amines of generalformula (V) which are used to prepare the above compounds, of formula(Ia), (Ia-1), (Ib), (Ic), (Ic-1), (Id), (Id-1), (Ie), (Ie-1), (Ik), (In)and (Ip). For compounds in which R⁶ is methyl, the configuration at thecarbon atom marked 2 is racemic i.e. (2RS).

TABLE 15 Physical data mp/opt. rot./ Cpd R⁶ R⁷ R⁸ R⁹ R¹⁰ A appearance15.1 H H H H H direct bond 15.2 H H H Me H direct bond HCl salt solid15.3 H H H F H direct bond HCl salt solid (a) 15.4 H H H Cl H directbond 15.5 H H H Br H direct bond 15.6 H Me H Me H direct bond 15.7 H HMe Me H direct bond (b) 15.8 H H H Me Me direct bond (c) 15.9 H H F Me Hdirect bond (d) 15.10 H H Cl Cl H direct bond 15.11 H H H H H CH₂ 15.12H H H Me H CH₂ HCl salt solid mp >260° C. (e) 15.13 H H H F H CH₂ 15.14H H H Cl H CH₂ 15.15 H H H Br H CH₂ 15.16 H Me H Me H CH₂ HCl salt solidmp 254-268° C. (f) 15.17 H H Me Me H CH₂ 15.18 H H H Me Me CH₂ 15.19 H HF Me H CH₂ 15.20 H H Cl Cl H CH₂ 15.21 H H H H H O 15.22 H H H Me H OHCl salt solid mp >260° C. (g) 15.23 H H H F H O 15.24 H H H Cl H O15.25 H H H Br H O 15.26 H Me H Me H O 15.27 H H Me Me H O 15.28 H H HMe Me O 15.29 H H F Me H O 15.30 H H Cl Cl H O 15.31 Me H H H H directbond 15.32 Me H H Me H direct bond 15.33 Me H H F H direct bond 15.34 MeH H Cl H direct bond 15.35 Me H H Br H direct bond 15.36 Me Me H Me Hdirect bond 15.37 Me H Me Me H direct bond 15.38 Me H H Me Me directbond 15.39 Me H F Me H direct bond 15.40 Me H Cl Cl H direct bond 15.41Me H H H H CH₂ 15.42 Me H H Me H CH₂ 15.43 Me H H F H CH₂ 15.44 Me H HCl H CH₂ 15.45 Me H H Br H CH₂ 15.46 Me Me H Me H CH₂ 15.47 Me H Me Me HCH₂ 15.48 Me H H Me Me CH₂ 15.49 Me H F Me H CH₂ 15.50 Me H Cl Cl H CH₂15.51 Me H H H H O 15.52 Me H H Me H O 15.53 Me H H F H O 15.54 Me H HCl H O 15.55 Me H H Br H O 15.56 Me Me H Me H O 15.57 Me H Me Me H O15.58 Me H H Me Me O 15.59 Me H F Me H O 15.60 Me H Cl Cl H O 15.61 H HH Et H direct bond HCl salt solid mp >260° C. (h) 15.62 H F H H H O HClsalt solid (i) 15.63 H Me Me H H O HCl salt solid mp 241-245° C. (j)15.64 H H H OMe H direct bond HCl salt solid Notes to references (a) to(k) in Table 15: (a) 1H-NMR (DMSO) 8.8 (br, 3H), 7.5 (m, 1H), 7.3 (m,1H), 7.1 (m, 1H), 4.7 (m, 1H), 3.0 (m, 1H), 2.8 (m, 1H), 2.5 (m, 1H),2.0 (m, 1H); (b) 7.14 (s, 1H), 6.98 (s, 1H), 4.30 (t, 1H), 2.87 (ddd,1H), 2.72 (m, 1H), 2.45 (m, 1H), 2.25 (s, 3H), 2.24 (s, 3H), 1.62 (m,1H); (c) 7.03 (d, 1H), 6.99 (d, 1H), 4.50 (dd, 1H), 3.12 (m, 1H), 2.79(ddd, 1H), 2.38 (m, 1H), 2.30 (s, 3H), 2.25 (s, 3H), 1.88 (m, 1H); (d)7.12 (d, 1H), 6.83 (d, 1H), 4.30 (t, 1H), 2.90 (ddd, 1H), 2.75 (m, 1H),2.50 (m, 1H), 2.24 (s, 3H), 1.64 (m, 1H); (e) (DMSO) 8.5 (br, 3H), 7.4(s, 1H), 7.1 (m, 2H), 4.3 (t, 1H), 2.7 (m, 2H), 2.25 (s, 3H), 2.1-1.6(m, 4H); (f) (DMSO) 8.4 (br, 3H), 7.15 (s, 1H), 6.95 (s, 1H), 4.3 (br,1H), 2.5 (m, 2H), 2.25 (s, 3H), 2.15 (s, 3H), 2.0-1.6 (m, 4H); (g)(DMSO) 8.8 (br, 3H), 7.4 (d, 1H), 7.05 (dd, 1H), 6.75 (d, 1H), 4.4 (br,1H), 4.2 (m, 2H), 2.25 (s, 3H), 2.3-2.0 (m, 2H); (h) (DMSO) 8.6 (br,3H), 7.5 (s, 1H), 7.2 (dd, 2H), 4.7 (t, 1H), 3.0 (m, 1H), 2.8 (m, 1H),2.6 (q, 2H), 2.5 (m, 1H), 2.0 (m, 1H), 1.2 (t, 3H); (i) (DMSO) 8.9 (br,3H), 7.4 (d, 1H), 7.2 (m, 1H), 6.95 (m, 1H), 4.5 (t, 1H), 4.3 (m, 2H),2.4-2.1 (m, 2H; (j) (DMSO) 8.7 (br, 3H), 7.3 (d, 1H), 6.75 (d, 1H), 4.4(t, 1H), 4.3 (m, 2H), 2.2 (s, 3H), 2.3-2.1 (m, 2H), 2.0 (s, 3H).

The following Table 16 illustrates the intermediate amines of the abovegeneral formula (Va) which are used to prepare the above compounds offormula (If), (If-1), (Ig), (Ig-1), (Ij), (Ij-1) and (IL).

TABLE 16 Cpd R⁶ R⁷ R⁸ R⁹ R¹⁰ A Physical data 16.1 Me H H H H direct bondHCl salt solid (a) 16.2 Me H H Me H direct bond HCl salt solid (b) 16.3Me H H F H direct bond 16.4 Me H H Cl H direct bond 16.5 Me H H Br Hdirect bond 16.6 Me Me H Me H direct bond 16.7 Me H Me Me H direct bond16.8 Me H H Me Me direct bond 16.9 Me H F Me H direct bond 16.10 Me H ClCl H direct bond 16.11 Me H H H H CH₂ HCl salt solid mp 246-247° C. (c)16.12 Me H H Me H CH₂ 16.13 Me H H F H CH₂ 16.14 Me H H Cl H CH₂ 16.15Me H H Br H CH₂ 16.16 Me Me H Me H CH₂ 16.17 Me H Me Me H CH₂ 16.18 Me HH Me Me CH₂ 16.19 Me H F Me H CH₂ 16.20 Me H Cl Cl H CH₂ 16.21 Me H H HH O HCl salt solid 16.22 Me H H Me H O 16.23 Me H H F H O 16.24 Me H HCl H O 16.25 Me H H Br H O 16.26 Me Me H Me H O 16.27 Me H Me Me H O16.28 Me H H Me Me O 16.29 Me H F Me H O 16.30 Me H Cl Cl H O Notes toreferences (a) to (c) in Table 16: (a) (DMSO) 8.8 (br, 3H), 7.7 (d, 1H),7.3 (m, 3H), 4.3 (br, 1H), 3.2 (m, 1H), 2.5 (m, 2H), 1.2 (d, 3H); (b)(DMSO) 8.8 (br, 3H), 7.4 (s, 1H), 7.15 (m, 2H), 4.2 (br, 1H), 3.2 (m,1H), 2.5 (m, 2H), 2.3 (s, 3H), 1.2 (d, 3H); (c) (DMSO) 8.5 (br, 3H), 7.6(dd, 1H), 7.2 (m, 3H), 4.1 (br, 1H), 2.8 (m, 1H), 2.2 (m, 1H), 2.0 (m,1H), 1.5 (m, 1H), 1.1 (d, 3H).

The following Table 17 illustrates the intermediate amines of the abovegeneral formula (Vb) which are used to prepare the above compounds offormula (Ih), (Ih-1), (Ii), (Ii-1) and (Im).

TABLE 17 Cpd R⁶ R⁷ R⁸ R⁹ R¹⁰ A Physical data 17.1 Me H H H H direct bondHCl salt solid mp 245-260° C. 17.2 Me H H Me H direct bond 17.3 Me H H FH direct bond 17.4 Me H H Cl H direct bond 17.5 Me H H Br H direct bond17.6 Me Me H Me H direct bond 17.7 Me H Me Me H direct bond 17.8 Me H HMe Me direct bond 17.9 Me H F Me H direct bond 17.10 Me H Cl Cl H directbond 17.11 Me H H H H CH₂ 17.12 Me H H Me H CH₂ 17.13 Me H H F H CH₂17.14 Me H H Cl H CH₂ 17.15 Me H H Br H CH₂ 17.16 Me Me H Me H CH₂ 17.17Me H Me Me H CH₂ 17.18 Me H H Me Me CH₂ 17.19 Me H F Me H CH₂ 17.20 Me HCl Cl H CH₂ 17.21 Me H H H H O 17.22 Me H H Me H O 17.23 Me H H F H O17.24 Me H H Cl H O 17.25 Me H H Br H O 17.26 Me Me H Me H O 17.27 Me HMe Me H O 17.28 Me H H Me Me O 17.29 Me H F Me H O 17.30 Me H Cl Cl H O

TABLES 18 and 19 Compounds of formula (XIII) (XIII)

in which R¹¹ is chloroacetyl [compounds no. 18.1 to 18.63] ormethoxyacetyl [compounds no. 19.1 to 19.63] and in case of compounds inwhich R⁶ is methyl, the configuration at the carbon atom marked 2 isracemic i.e. (2RS). Physical data mp/opt. rot./ Cpd Cpd R⁶ R⁷ R⁸ R⁹ R¹⁰A appearance 18.1 19.1 H H H H H direct bond 18.2 19.2 H H H Me H directbond 18.3 19.3 H H H F H direct bond 18.4 19.4 H H H Cl H direct bond18.5 19.5 H H H Br H direct bond 18.6 19.6 H Me H Me H direct bond 18.719.7 H H Me Me H direct bond 18.8 19.8 H H H Me Me direct bond 18.9 19.9H H F Me H direct bond 18.10 19.10 H H Cl Cl H direct bond 18.11 19.11 HH H H H CH₂ 18.12 19.12 H H H Me H CH₂ 18.13 19.13 H H H F H CH₂ 18.1419.14 H H H Cl H CH₂ 18.15 19.15 H H H Br H CH₂ 18.16 19.16 H Me H Me HCH₂ 18.17 19.17 H H Me Me H CH₂ 18.18 18.18 H H H Me Me CH₂ 18.19 19.19H H F Me H CH₂ 18.20 19.20 H H Cl Cl H CH₂ 18:21 19.21 H H H H H O 18.2219.22 H H H Me H O 18.23 19.23 H H H F H O 18.24 19.24 H H H Cl H O18.25 19.25 H H H Br H O 18.26 19.26 H Me H Me H O 18.27 19.27 H H Me MeH O 18.28 19.28 H H H Me Me O 18.29 19.29 H H F Me H O 18.30 19.30 H HCl Cl H O 18.31 19.31 Me H H H H direct bond 18.32 19.32 Me H H Me Hdirect bond 18.33 19.33 Me H H F H direct bond 18.34 19.34 Me H H Cl Hdirect bond 18.35 19.35 Me H H Br H direct bond 18.36 19.36 Me Me H Me Hdirect bond 18.37 19.37 Me H Me Me H direct bond 18.38 19.38 Me H H MeMe direct bond 18.39 19.39 Me H F Me H direct bond 18.40 19.40 Me H ClCl H direct bond 18.41 19.41 Me H H H H CH₂ 18.42 19.42 Me H H Me H CH₂18.43 19.43 Me H H F H CH₂ 18.44 19.44 Me H H Cl H CH₂ 18.45 19.45 Me HH Br H CH₂ 18.46 19.46 Me Me H Me H CH₂ 18.47 19.47 Me H Me Me H CH₂18.48 19.48 Me H H Me Me CH₂ 18.49 19.49 Me H F Me H CH₂ 18.50 19.50 MeH Cl Cl H CH₂ 18.51 19.51 Me H H H H O 18.52 19.52 Me H H Me H O 18.5319.53 Me H H F H O 18.54 19.54 Me H H Cl H O 18.55 19.55 Me H H Br H O18.56 19.56 Me Me H Me H O 18.57 19.57 Me H Me Me H O 18.58 19.58 Me H HMe Me O 18.59 19.59 Me H F Me H O 18.60 19.60 Me H Cl Cl H O 18.61 19.61H H H Et H direct bond 18.62 19.62 H F H H H O 18.63 19.63 H Me Me H H O

TABLES 20 and 21 Compounds of formula (XIIIa) (XIIIa)

in which R¹¹ is chloroacetyl [compounds no. 20.1 to 20.30] ormethoxyacetyl [compounds no. 21.1 to 21.30] Cpd Cpd R⁶ R⁷ R⁸ R⁹ R¹⁰ APhysical data 20.1 21.1 Me H H H H direct bond 20.2 21.2 Me H H Me Hdirect bond 20.3 21.3 Me H H F H direct bond 20.4 21.4 Me H H Cl Hdirect bond 20.5 21.5 Me H H Br H direct bond 20.6 21.6 Me Me H Me Hdirect bond 20.7 21.7 Me H Me Me H direct bond 20.8 21.8 Me H H Me Medirect bond 20.9 21.9 Me H F Me H direct bond 20.10 21.10 Me H Cl Cl Hdirect bond 20.11 21.11 Me H H H H CH₂ 20.12 21.12 Me H H Me H CH₂ 20.1321.13 Me H H F H CH₂ 20.14 21.14 Me H H Cl H CH₂ 20.15 21.15 Me H H Br HCH₂ 20.16 21.16 Me Me H Me H CH₂ 20.17 21.17 Me H Me Me H CH₂ 20.1821.18 Me H H Me Me CH₂ 20.19 21.19 Me H F Me H CH₂ 20.20 21.20 Me H ClCl H CH₂ 20.21 21.21 Me H H H H O 20.22 21.22 Me H H Me H O 20.23 21.23Me H H F H O 20.24 21.24 Me H H Cl H O 20.25 21.25 Me H H Br H O 20.2621.26 Me Me H Me H O 20.27 21.27 Me H Me Me H O 20.28 21.28 Me H H Me MeO 20.29 21.29 Me H F Me H O 20.30 21.30 Me H Cl Cl H O

TABLES 22 and 23 Compounds of formula (XIIIb) (XIIIb)

in which R¹¹ is chloroacetyl [compounds no. 22.1 to 22.30] ormethoxyacetyl [compounds no. 23.1 to 23.30] Cpd Cpd R⁶ R⁷ R⁸ R⁹ R¹⁰ APhysical data 22.1 23.1 Me H H H H direct bond 22.2 23.2 Me H H Me Hdirect bond 22.3 23.3 Me H H F H direct bond 22.4 23.4 Me H H Cl Hdirect bond 22.5 23.5 Me H H Br H direct bond 22.6 23.6 Me Me H Me Hdirect bond 22.7 23.7 Me H Me Me H direct bond 22.8 23.8 Me H H Me Medirect bond 22.9 23.9 Me H F Me H direct bond 22.10 23.10 Me H Cl Cl Hdirect bond 22.11 23.11 Me H H H H CH₂ 22.12 23.12 Me H H Me H CH₂ 22.1323.13 Me H H F H CH₂ 22.14 23.14 Me H H Cl H CH₂ 22.15 23.15 Me H H Br HCH₂ 22.16 23.16 Me Me H Me H CH₂ 22.17 23.17 Me H Me Me H CH₂ 22.1823.18 Me H H Me Me CH₂ 22.19 23.19 Me H F Me H CH₂ 22.20 23.20 Me H ClCl H CH₂ 22.21 23.21 Me H H H H O 22.22 23.22 Me H H Me H O 22.23 23.23Me H H F H O 22.24 23.24 Me H H Cl H O 22.25 23.25 Me H H Br H O 22.2623.26 Me Me H Me H O 22.27 23.27 Me H Me Me H O 22.28 23.28 Me H H Me MeO 22.29 23.29 Me H F Me H O 20.30 23.30 Me H Cl Cl H O

According to a further feature of the present invention, there isprovided the use as a herbicide or plant growth regulator characterisedin that the compound of formula (I) or a salt thereof is applied in aneffective amount for the control of weeds or for regulating the growthof plants at a plant locus. For this purpose, the said compound isnormally used in the form of a herbicidal composition (i.e. inassociation with compatible diluents or carriers and/or surface activeagents suitable for use in herbicidal compositions), for example ashereinafter described.

By application to the ‘plant locus’ is meant application, for example tothe plant growing medium, such as soil, as well as to the seeds,emerging seedlings, roots, stems, leaves or other plant parts.

The compounds of the formula (I) and their salts, all termed hereinbelowas compounds of formula (I), have an excellent herbicidal activityagainst a broad range of economically important monocotyledonous anddicotyledonous harmful plants. The compounds of formula (I) also actefficiently on perennial weeds which produce shoots from rhizomes, rootstocks or other perennial organs and which are difficult to control. Inthis context, the substances can be applied pre-planting, pre-emergenceor post-emergence.

Specifically, examples may be mentioned of some representatives of themonocotyledonous and dicotyledonous weed flora which can be controlledby the compounds of formula (I), without the enumeration being arestriction to certain species.

Amongst the monocotyledonous weed species, those on which the activesubstances act efficiently are, for example, Agrostis, Alopecurus,Apera, Avena, Brachicaria, Bromus, Dactyloctenium, Digitaria,Echinochloa, Eleocharis, Eleusine, Festuca, Fimbristylis, Ischaemum,Lolium, Monochoria, Panicum, Paspalum, Phalaris, Phleum, Poa,Sagittaria, Scirpus, Setaria, Sphenoclea and Cyperus species from theannual group and, amongst the perennial species, Agropyron, Cynodon,Imperata and Sorghum and also perennial Cyperus species.

In the case of dicotyledonous weed species, the spectrum of actionextends to species such as, for example, Galium, Viola, Veronica,Lamium, Stellaria, Amaranthus, Sinapis, Ipomoea, Matricaria, Abutilonand Sida amongst the annuals and Convolvulus, Cirsium, Rumex andArtemisia in the case of the perennial weeds.

Herbicidal action is also achieved in the case of dicotyledonous harmfulplants such as Ambrosia, Anthemis, Carduus, Centaurea, Chenopodium,Datura, Emex, Galeopsis, Galinsoga, Kochia, Lepidium, Lindernia,Papaver, Portlaca, Polygonum, Ranunculus, Rorippa, Rotala, Seneceio,Sesbania, Solanum, Sonchus, Taraxacum, Trifolium, Urtica and Xanthium.

Harmful plants occurring under the specific cultivation conditions ofrice, such as, for example, Sagittaria, Alisma, Eleocharis, Scirpus andCyperus, are also well controlled by the active substances according tothe invention.

If the compounds according to the invention are applied to the soilsurface before germination (pre-emergence of the weeds), then the weedseedlings are either prevented completely from emerging or the weedsgrow until they have reached the cotyledon stage, but then their growthstops and they finally die completely after three to four weeks haveelapsed.

When the active substances are applied post-emergence to the green,parts of the plants, growth stops equally drastically a very short timeafter treatment and the weed plants remain at the stage of growth at thetime of application, or they die completely after a certain time, sothat in this manner competition by the weeds, which is harmful to thecrop plants, is eliminated at a very early stage and in a sustainedmanner.

Although the compounds according to the invention have an excellentherbicidal activity against mono- and dicotyledonous weeds, some cropplants of economically important crops such as, for example, wheat,barley, rye, triticale, rice, maize, sugar beet, cotton or soybeans(particularly wheat, barley, rice or maize) are damaged only to aninsignificant extent or not at all, if an appropriate dosage is applied.For these reasons, the present compounds are in some cases suitable forthe selective control of undesired vegetation in stands ofagriculturally useful plants or in stands of ornamental plants.

The activity allows to employ the compounds as effective herbicidalactive ingredients pre- and post-emergence for controlling broad-leavedweeds and grass weeds at relatively low dosage as a selective herbicidein some crops (preferably pre-emergence of the weeds in many cases).Alternatively the compounds can be used effectively at some higherdosage for the control of a broad range of dicotyledonous weeds andmonocotyledonous weeds in plantation crops and on uncultivated land and,by means of specific application techniques, also for inter-rowtreatment in agricultural row crops such as maize, cotton and the like.

The compositions according to the invention can be used to selectivelycontrol annual and perennial harmful plants in plantation crops such asoil palm, coconut palm, India-rubber tree, citrus, pineapples, pome,cotton, coffee, cocoa and the like, as well as in fruit production andviticulture. Equally, the combinations according to the invention can beemployed in arable crop production using the no-till or zero-tillmethod.

Another object of the invention is thus the selective weed control inplantation crops by applying the compounds according to the invention asherbicides.

Alternatively, they can be used as very effective herbicides in anon-selective manner on paths, open spaces and industrial sites and thelike to keep these areas free from undesirable vegetation.

The herbicidal compositions according to the invention are distinguishedby a long-term herbicidal action with a rapid onset.

It is also possible to use the compounds (I) in combination with otherpesticidally active substances or nutrients, such as, for example,insecticides, acaricides, herbicides, fungicides, safeners, fertilizersand/or growth regulators.

The invention thus also relates to a method of controlling undesirablevegetation which comprises applying one or more type A herbicidestogether with one or more type B herbicides and a type C surfactant tothe harmful plants, parts of these plants or the area under cultivation.Type A herbicides are the compounds of formula (I) or their salts; typeB herbicides are other herbicides useful to be combined with compounds(I) for the purpose of broadening weed spectrum to be controlled, orincreasing herbicidal effect (some possible type B herbicides arementioned further below).

In addition, the substances according to the invention have outstandinggrowth-regulatory properties in crop plants. They engage in the plants'metabolism in a regulatory fashion and can thus be employed forinfluencing plant constituents in a targeted fashion and forfacilitating harvesting, such as, for example, by triggering desiccationand stunted growth. Moreover, they are also suitable for generallycontrolling and inhibiting undesired vegetative growth withoutsimultaneously killing the plants. Inhibiting vegetative growth plays animportant role in many monocotyledonous and dicotyledonous crops sincelodging can be reduced, or prevented completely, hereby.

Due to their herbicidal and plant-growth regulatory properties, thecompounds of formula (I) can also be employed for controlling harmfulplants in crops of known genetically modified plants, or geneticallymodified plants yet to be developed. As a rule, the transgenic plantsare distinguished by particular advantageous properties, for example byresistances to certain pesticides, mainly certain herbicides,resistances to plant diseases or pathogens of plant diseases, such ascertain insects, or microorganisms such as fungi, bacteria or viruses.Other particular properties relate, for example, to the harvestedmaterial with regard to quantity, quality, storage properties,composition and specific constituents. Thus, transgenic plants are knownwhere the starch content is increased or the starch quality is alteredor those where the harvested material has a different fatty acidspectrum.

The compounds of formula (I) are preferably employed in economicallyimportant transgenic crops of useful plants and ornamentals, for examplecereals such as wheat, barley, rye; oats, sorghum and millet, rice,cassaya and maize, or else crops of sugar beet, cotton, soya, oil seedrape, potatoes, tomatoes, peas and other vegetables. The compounds offormula (I) can preferably be employed as herbicides in crops of usefulplants which are resistant to the phytotoxic effects of the herbicidesor have been rendered thus by means of genetic engineering.

Traditional ways of generating novel plants which have modifiedcharacteristics in comparison with existing plants consist, for example,in traditional breeding methods and the generation of mutants. However,it is also possible to generate novel plants with alteredcharacteristics with the aid of genetic engineering methods (see, forexample, EP-A-0221044, EP-A-0131624). For example, several cases havebeen described of

-   -   genetic engineering modifications of crop plants with the        purpose of modifying the starch synthesized in the plants (for        example WO 92/11376, WO 92/14827, WO 91/19806),    -   transgenic crop plants, which are resistant to certain        herbicides of the glufosinate type (cf., for example,        EP-A-0242236, EP-A-242246) or the glyphosate type (WO 92/00377)        or the sulfonylurea type (EP-A-0257993, U.S. Pat. No.        5,013,659),    -   transgenic crop plants, for example cotton, which are capable of        producing Bacillus thuringiensis toxins (Bt toxins) which make        the plants resistant to specific pests (EP-A-0142924,        EP-A-0193259),    -   transgenic crop plants whose fatty acid spectrum is modified (WO        91/13972).

A large number of techniques in molecular biology by means of whichnovel transgenic plants with altered characteristics can be generatedare known in principle; see, for example, Sambrook et al., 1989,Molecular Cloning, A Laboratory Manual, 2nd Ed, Cold Spring HarborLaboratory Press, Cold Spring Harbor, N.Y.; or Winnacker “Gene andKlone” [Genes and Clones], VCH Weinheim 2nd Edition 1996, or Christou,“Trends in Plant Science” 1 (1996) 423-431).

In order to perform such genetic engineering manipulations, nucleic acidmolecules may be introduced into plasmids which allow mutagenesis or asequence change by means of recombination of DNA sequences. It ispossible, for example, with the aid of the abovementioned standardmethods to perform base exchanges, to remove subsequences or to addnatural or synthetic sequences. To connect the DNA fragments to eachother, adaptors or linkers may be attached to the fragments.

For example, plant cells with a reduced activity of a gene product canbe generated by expressing at least one corresponding antisense RNA, asense RNA to achieve a cosuppressory effect or by expressing at leastone ribozyme of suitable construction which specifically cleavestranscripts of the abovementioned gene product.

To this end it is possible to make use of, on the one hand, DNAmolecules which encompass the entire coding sequence of a gene productinclusive of any flanking sequences which may be present, on the otherhand DNA molecules which only encompass parts of the coding sequence,but these parts must be long enough in order to effect, in the cells, anantisense effect. Use may also be made of DNA sequences which show ahigh degree of homology to the coding sequences of a gene product; butwhich, are not completely identical.

When nucleic acid molecules are expressed in plants, the protein whichhas been synthesized, may be located in any desired compartment of theplant cell. However, to achieve localization in a particularcompartment, it is possible, for example, to link the coding region withDNA sequences which guarantee localization in a particular compartment.Such sequences are known to the skilled worker (see, for example, Braunet al., EMBO J. 11 (1992), 3219-3227; Wolter et al., Proc. Natl. Acad.Sci. USA 85 (1988), 846-850; Sonnewald et al., Plant J. 1 (1991),95-106).

The transgenic plant cells may be regenerated by known techniques togive complete plants. In principle, the transgenic plants can be plantsof any desired plant species, that is to say monocotyledonous and alsodicotyledonous plants.

This allows transgenic plants to be obtained which exhibit alteredcharacteristics by means of overexpression, suppression or inhibition ofhomologous (=natural) genes or gene sequences or by means of expressionof heterologous (=foreign) genes or gene sequences.

The compounds of formula (I) can preferably be employed in transgeniccrops which are resistant to herbicides from the group of thesulfonylureas, glufosinate-ammonium or glyphosate-isopropylammonium andanalogous active substances.

When the compounds of formula (I) are used in transgenic crops, effectsother than the herbicidal effects to be observed in other crops arefrequently found which are specific for application in the particulartransgenic crop, for example an altered or specifically widened weedspectrum which can be controlled, altered application rates which may beemployed for application, preferably good combining ability with theherbicides to which the transgenic crop is resistant, and an effect ongrowth and yield of the transgenic crop plants.

The invention therefore also relates to the use of the compounds offormula (I) as herbicides for controlling harmful plants in transgeniccrop plants.

The use according to the invention for controlling harmful plants or forregulating the growth of plants also includes the case where thecompounds of formula (I) are only formed in the plant or the soil from aprecursor (“prodrug”) after its application to the plant.

The compounds of formula (I) can be employed in the conventionalpreparations as wettable powders, emulsifiable concentrates, sprayablesolutions, dusts or granules. The invention therefore also relates toherbicidal and plant-growth-regulating compositions which comprisecompounds of formula (I).

According to a further feature of the present invention, there isprovided a herbicidal or plant growth regulating composition comprisingan effective amount of a compound of formula (I) as defined above or anagriculturally acceptable salt thereof, in association with, andpreferably homogeneously dispersed in, one or more compatibleagriculturally-acceptable diluents or carriers and/or surface activeagents [i.e. diluents or carriers and/or surface active agents of thetype generally accepted in the art as being suitable for use inherbicidal compositions and which are compatible with compounds of theinvention]. The term “homogeneously dispersed” is used to includecompositions in which the compounds of formula (I) are dissolved inother components. The term “herbicidal compositions” is used in a broadsense to include not only compositions which are ready for use asherbicides but also concentrates which must be diluted before use(including tank mixtures).

The compounds of formula (I) can be formulated in various ways,depending on the prevailing biological and/or chemico-physicalparameters. Examples of possible formulations which are suitable are:wettable powders (WP), water-soluble powders (SP), water-solubleconcentrates, emulsifiable concentrates (EC), emulsions (EW) such asoil-in-water and water-in-oil emulsions, sprayable solutions, suspensionconcentrates (SC), dispersions on an oil or water basis, solutions whichare miscible with oil, capsule suspensions (CS), dusts (DP),seed-dressing products, granules for broadcasting and soil application,granules (GR) in the form of microgranules, spray granules, coatedgranules and adsorption granules, water-dispersible granules (WG),water-soluble granules (SG), ULV formulations, microcapsules and waxes.

These individual formulation types are known in principle and described,for example, in: Winnacker-Küchler, “Chemische Technologie” [ChemicalTechnology], Volume 7, C. Hauser Verlag, Munich, 4th Edition 1986; Wadevan Valkenburg, “Pesticide Formulations”, Marcel Dekker, N.Y., 1973; K.Martens, “Spray Drying Handbook”, 3rd Ed. 1979, G. Goodwin Ltd. London.

The necessary formulation auxiliaries such as inert materials,surfactants, solvents and other additives are also known and described,for example, in: Watkins, “Handbook of Insecticide Dust Diluents andCarriers”, 2nd Ed., Darland Books, Caldwell N.J.; H. v. Olphen,“Introduction to Clay Colloid Chemistry”, 2nd Ed., J. Wiley & Sons,N.Y.; C. Marsden, “Solvents Guide”, 2nd Ed., Interscience, N.Y. 1963;McCutcheon's “Detergents and Emulsifiers Annual”, MC Publ. Corp.,Ridgewood. N.J.; Sisley and Wood, “Encyclopedia of Surface ActiveAgents”, Chem. Publ. Co. Inc., N.Y. 1964; Schönfeldt,“Grenzflächenaktive Äthylenoxidaddukte” [Surface-active ethylene oxideadducts], Wiss. Verlagsgesell., Stuttgart. 1976; Winnacker-Küchler,“Chemische Technologie” [Chemical Technology], Volume 7, C. HauserVerlag, Munich, 4th Ed. 1986.

Based on these formulations, it is also possible to prepare combinationswith other pesticidally active substances such as, for example,insecticides, acaricides, herbicides, fungicides, and with safeners,fertilizers and/or growth regulators, for example in the form of areadymix or a tank mix.

Wettable powders are preparations which are uniformly dispersible inwater and which, besides the compounds of, formula (I), also compriseionic and/or nonionic surfactants (wetters, dispersants), for example,polyoxyethylated alkylphenols, polyoxyethylated fatty alcohols,polyoxyethylated fatty amines, fatty alcohol polyglycol ether sulfates,alkanesulfonates or alkylbenzenesulfonates, sodium lignosulfonate,sodium 2,2′-dinaphthylmethane-6,6′-disulfonate, sodiumdibutylnaphthalenesulfonate or else sodium oleoylmethyltaurinate, inaddition to a diluent or inert substance. To prepare the wettablepowders, the compounds of formula (I) are, for example, ground finely inconventional apparatuses such as hammer mills, blower mills and air-jetmills and mixed with the formulation auxiliaries, either concomitantlyor thereafter.

Emulsifiable concentrates are prepared, for example, by dissolving thecompounds of formula (I) in an organic solvent, for example butanol,cyclohexanone, dimethylformamide, xylene or else higher-boilingaromatics or hydrocarbons or mixtures of these, with addition of one ormore ionic and/or nonionic surfactants (emulsifiers). Emulsifiers whichcan be used are, for example: calcium salts of alkylarylsulfonic acids,such as calcium dodecylbenzenesulfonate or nonionic emulsifiers, such asfatty acid polyglycol esters, alkylaryl polyglycol ethers, fatty alcoholpolyglycol ethers, propylene oxide/ethylene oxide condensates, alkylpolyethers, sorbitan esters such as sorbitan fatty acid: esters orpolyoxyethylene sorbitan esters such as polyoxyethylene sorbitan fattyacid esters.

Dusts are obtained by grinding the active substance with finely dividedsolid substances, for example talc or natural clays, such as kaolin,bentonite or pyrophyllite, or diatomiceous earth.

Suspension concentrates may be water- or oil-based. They can beprepared, for example, by wet grinding by means of commerciallyavailable bead mills, if appropriate with addition of surfactants, asthey have already been mentioned above for example in the case of theother formulation types.

Emulsions, for example oil-in-water emulsions (EW), can be prepared forexample by means of stirrers, colloid mills and/or static mixtures usingaqueous organic solvents and, if appropriate, surfactants as they havealready been mentioned above for example in the case of the otherformulation types.

Granules can be prepared either by spraying the compounds of formula (I)onto adsorptive, granulated inert material or by applying activesubstance concentrates onto the surface of carriers such as sand,kaolinites or of granulated inert material, by, means of binders, orexample polyvinyl alcohol, sodium polyacrylate or alternatively mineraloils. Suitable active substances can also be granulated in the mannerwhich is conventional for the production of fertilizer granules, ifdesired in a mixture with fertilizers.

Water-dispersible granules are prepared, as a rule, by the customaryprocesses such as spray-drying, fluidized-bed granulation, diskgranulation, mixing in high-speed mixers and extrusion without solidinert material. To prepare disk, fluidized-bed, extruder and spraygranules, see, for example, processes in “Spray-Drying Handbook” 3rd ed.1979, G. Goodwin Ltd., London; J. E. Browning, “Agglomeration”, Chemicaland Engineering 1967, pages 147 et seq.; “Perry's Chemical Engineer'sHandbook”, 5th Ed., McGraw-Hill, New York 1973, p. 8-57.

For further details on the formulation of crop protection products, see,for example, G. C. Klingman, “Weed Control as a Science”, John Wiley andSons, Inc., New York, 1961, pages 81-96 and J. D. Freyer, S. A. Evans,“Weed Control Handbook”, 5th Ed., Blackwell Scientific Publications,Oxford, 1968, pages 101-103.

As a rule, the agrochemical preparations comprise 0.1 to 99% by weight,in particular 0.1 to 95%, by weight, of compounds of formula (I).

The concentration of compounds of formula (I) in wettable powders is,for example, approximately 10 to 90% by weight, the remainder to 100% byweight being composed of customary formulation components. In the caseof emulsifiable concentrates, the concentration of compounds of formula(I) can amount to approximately 1 to 90, preferably 5 to 80% by weight.Formulations in the form of dusts usually comprise 1 to 30% by weight ofcompounds of formula (I), preferably in most cases 5 to 20% by weight ofcompounds of formula (I), while sprayable solutions compriseapproximately 0.05 to 80, preferably 2 to 50% by weight of compounds offormula (I). In the case of water-dispersible granules, the content ofcompounds of formula (I) depends partly on whether the compounds offormula (I) are in liquid or solid form and on which granulationauxiliaries, fillers and the like are being used. The water-dispersiblegranules, for example, comprise between 1 and 95% by weight of activesubstance, preferably between 10 and 80% by weight.

In addition, the formulations of compounds of formula (I) mentionedcomprise, if appropriate, the adhesives, wetters, dispersants,emulsifiers, penetrants, preservatives, antifreeze agents, solvents,fillers, carriers, colorants, antifoams, evaporation inhibitors, pHregulators and viscosity regulators which are conventional in each case.

The compounds of the formula (I) or their salts can be employed as suchor in the form of their preparations (formulations) as combinations withother pesticidally active substances, such as, for example,insecticides, acaricides, nematicides, herbicides, fungicides, safeners,fertilizers and/or growth regulators, for example as a premix or as tankmixes.

Components which may be employed for the active substances according tothe invention in mixed formulations nor in tank mix are, for example,known active compounds which are based on an inhibition of, for example,acetolactate synthase, acetyl-coenzyme A carboxylase, PS I, PS II,HPPDO, phytoene desaturase, protoporphyrinogen oxidase, glutaminesynthetase, cellulose biosynthesis, 5-enolpyruvylshikimate-3-phosphatesynthetase. Such compounds, and also other compounds which can beemployed, whose mechanism of action is to a degree unknown or different,are described, for example, in Weed Research 26, 441-445 (1986), or “ThePesticide Manual”, 12th Edition 2000 (hereinbelow also abbreviated to“PM”), The British Crop Protection Council and the Royal Soc. ofChemistry (editors), including the e-Pesticide Manual Version 2.2(2002), and literature cited therein. Herbicides which are known fromthe literature and which can be mentioned, which can be combined withthe compounds of the formula (I), are, for example, the following activesubstances (Note: the compounds are either designated by the common,name according to the International Organization for Standardization(ISO) or using the chemical: name, if appropriate together with acustomary code number); compounds having common names are also referredto in the “Compendium of Pesticide Common Names” available from theInternet, and the literature cited, therein: acetochlor;acifluorfen(-sodium); aclonifen; AKH 7088, i.e.[[[1-[5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrophenyl]-2-methoxyethylidene]amino]oxy]aceticacid and, its methyl ester; alechlor; alloxydim(-sodium); ametryn;amicarbazone, amidochlor, amidosulfuron; amitrol; AMS, i.e. ammoniumsulfamate; anilofos; asulam; atrazine; azafenidin; azimsulfuron(DPX-A8947); aziprotryn; barban; BAS 516 H, i.e.5-fluoro-2-phenyl-4H-3,1-benzoxazin-4-one; beflubutamid;benazolin(-ethyl); benfluralin; benfuresate; bensulfuron(-methyl);bensulide; bentazone(-sodium); benzobicyclone; benzofenap; benzofluor;benzoylprop(-ethyl); benzthiazuron; bialaphos (bilanafos); bifenox;bispyribac(-sodium); bromacil; bromobutide; bromofenoxim; bromoxynil;bromuron; buminafos; busoxinone; butachlor; butafenacil; butamifos;butenachior; buthidazole; butralin; butroxydim; butylate; cafenstrole(CH-900); carbetamide; carfentrazone(-ethyl); caloxydim, CDAA, i.e.2-chloro-N,N-di-2-propenylacetamide; CDEC, i.e. 2-chloroallyldiethyldithiocarbamate; chlomethoxyfen; chloramben; chlorazifop-butyl;chlorbromuron; chlorbufam; chlorfenac; chlorflurenol-methyl;chloridazon; chlorimuron(-ethyl); chlornitrofen; chlorotoluron;chloroxuron; chlorpropham; chlorsulfuron; chlorthal-dimethyl;chlorthiamid; chlortoluron, cinidon(-methyl or -ethyl), cinmethylin;cinosulfuron; clethodim; clefoxydim; clodinafop and its esterderivatives (for example clodinafop-propargyl); clomazone; clomeprop;cloproxydim; clopyralid; clopyrasulfuron(-methyl); cloransulam(-methyl);cumyluron (JC 940); cyanazine; cycloate; cyclosulfamuron (AC 104);cycloxydim; cycluron; cyhalofop and its ester derivatives (for examplebutyl-ester, DEH-112); cyperquat; cyprazine; cyprazole; daimuron; 2,4-D;2,4-DB; dalapon; dazomet, desmedipham; desmetryn; di-allate; dicamba;dichlobenil; dichlorprop(-P); diclofop and its esters such asdiclofop-methyl; diclosulam, diethatyl(-ethyl); difenoxuron;difenzoquat; diflufenican; diflufenzopyr; dimefuron; dimepiperate;dimethachlor; dimethametryn; dimethenamid (SAN-582H) dimethenamid(-P);dimethazone, dimethipin; dimexyflam, dimetrasulfuron, dinitramine;dinoseb; dinoterb; diphenamid; dipropetryn; diquat; dithiopyr; diuron;DNOC; eglinazine-ethyl; EL 77, i.e.5-cyano-1-(1,1-dimethylethyl)-N-methyl-1H-pyrazole-4-carboxamide;endothal; epoprodan, EPIC; esprocarb; ethalfluralin;ethametsulfuron-methyl; ethidimuron; ethiozin; ethofumesate; ethoxyfenand its esters; (for example ethyl ester, HC-252), ethoxysulfuron,etobenzanid (HW 52); F5231, i.e.N-[2-chloro-4-fluoro-5-[4-(3-fluoropropyl)-4,5-dihydro-5-oxo-1H-tetrazol-1-yl]-phenyl]ethanesulfonamide;fenoprop; fenoxan, fenoxaprop and fenoxaprop-P and their esters, forexample fenoxaprop-P-ethyl and fenoxaprop-ethyl; fenoxydim;fentrazamide; fenuron; flamprop(-methyl or -isopropyl or -isopropyl-L);flazasulfuron; florasulam; fluazifop and fluazifop-P and their esters,for example, fluazifop-butyl and fluazifop-P-butyl; fluazolate,flucarbazone(-sodium); fluchloralin; flufenacet (FOE 5043), flufenpyr,flumetsulam; flumeturom flumiclorac(-pentyl); flumioxazin (S-482);flumipropyn; fluometuron; fluorochloridone, fluorodifen;fluoroglycofen(-ethyl); flupoxam (KNW-739); flupropacil (UBIC-4243),fluproanate, flupyrsulfuron(-methyl, or -sodium); flurenol(-butyl);fluridone; fluorochloridone; fluoroxypyr(-meptyl); flurprimidol,flurtamone; fluthiacet(-methyl);fluthiamide (also known as flufenacet);fomesafen; foramsulfuron; fosamine; furilazole (MON 13900); furyloxyfen;glufosinate(-ammonium); glyphosate(=isopropyl-ammonium); halosafen;halosulfuron(-methyl) and its esters (for example the methyl ester,NC-319); haloxyfop and its esters; haloxyfop-P (=: R-haloxyfop) and itsesters; HC-252 (diphenylether), hexazinone; imazamethabenz(-methyl);imazamethapyr; imazamox; imazapic, imazapyr; imazaquin and salts such asthe ammonium, salts; imazethamethapyr; imazethapyr, imazosulfuron;indanofan; iodosulfuron-(methyl)-(sodium), ioxynil; isocarbamid;isopropalin; isoproturon; isouron; isoxaben; isoxachloriole;isoxaflutole; isoxapyrifop; karbutilate; lactofen; lenacil; linuromMCPA; MCPB; mecoprop; mefenacet; mefluidid; mesosulfuron(-methyl);mesotrione; metam, metamifop, metamitron; metazachlor;methabenzthiazuron; methazole; methoxyphenone; methyldymron;metobenzuron, metobromuron; (S-)metolachlor; metosulam (XRD 511);metoxurommetribuzin; metsulfuron-methyl; MK-616; molinate; monalide;monocarbamide dihydrogensulfate; monolinuron; monuron; MT 128, i.e.6-chloro-N-(3-chloro-2-propenyl)-5-methyl-N-phenyl-3-pyridazinamine; MT5950, i.e. N-[3-chloro-4-(1-methylethyl)-phenyl]-2-methylpentanamide;naproanilide; napropamide; naptalam; NC 310, i.e.4-(2,4-dichlorobenzoyl)-1-methyl-5-benzyloxypyrazole; neburon;nicosulfuron; nipyraclophen; nitralin; nitrofen; nitrofluorfen;norflurazon; orbencarb; oryzalin; oxadiargyl (RP-020630); oxadiazone;oxasulfuron; oxaziclomefone; oxyfluorfen; paraquat; pebulate; pelargonicacid; pendimethalin; penoxulam; pentanochlor, pentoxazone; perfluidone;pethoxamid, phenisopham; phenmedipham; picloram; picolinafen;piperophos; piributicarb; pirifenop-butyl; pretilachlor;primisulfuron(-methyl); procarbazone(-sodium); procyazine; prodiamine;profluazole, profluralin; proglinazine(-ethyl); prometon; prometryn;propachior; propanil; propaquizafop; propazine; propham; propisochior;propoxycarbazone(-sodium), propyzamide; prosulfalin; prosulfocarb;prosulfuron (CGA-152005); prynachlor; pyraclonil, pyraflufen(-ethyl);pyrazolinate; pyrazon; pyrazosulfuron(-ethyl); pyrazoxyfen;pyribenzoxim; pyributicarb; pyridefol; pyridate; pyriftalid,pyrimidobac(-methyl); pyrithiobac(-sodium) (KIH-2031); pyroxofop and itsesters (for example propargyl ester); quinclorac; quinmerac;quinoclamine, quinofop and its ester derivatives, quizalofop andquizalofop-P and their ester derivatives, for example quizalofop-ethyl;quizalofop-P-tefuryl, and -ethyl; renriduron; rimsulfuron (DPX-E 9636);S 275, i.e.2-[4-chloro-2-fluoro-5-(2-propynyloxy)phenyl]-4,5,6,7-tetrahydro-2H-indazole;secbumeton; sethoxydim; siduron; simazine; simetryn; SN 106279, i.e.2-[[7-[2-chloro-4-(trifluoromethyl)phenoxy]-2-naphthalenyl]oxy]propanoicacid and its methyl ester; sulcotrione; sulfentrazone (FMC-97285,F-6285); sulfazuron; sulfometuron(-methyl); sulfosate (ICI-A0224);sulfosulfuron; TCA; tebutam (GCP-5544); tebuthiuron; tepraloxydim;terbacil; terbucarb; terbuchlor; terbumeton; terbuthylazine; terbutryn;TFH 450,N,N-diethyl-3-[(2-ethyl-6-methylphenyl)sulfonyl]-1H-1,2,4-triazole-1-carboxamide;thenylchlor (NSK-850); thiafluamide; thiazafluoron; thiazopyr(Mon-13200); thidiazimin (SN-24085); thifensulfuron(-methyl);thiobencarb; tiocarbazil; tralkoxydim; tri-allate; triasulfuron;triaziflam; triazofenamide; tribenuron(-methyl); 2,8,6-trichlorobenzoicacid (2,3,6-TBA), triclopyr; tridiphane; trietazine;trifloxysulfuron(-sodium), trifluralin; triflusulfuron and esters (e.g.methyl ester, DPX-66037); trimeturon; tritosulfuron; tsitodef; vemolate;WL 110547, i.e. 5-phenoxy-1-[3-(trifluoromethyl)phenyl]-1H-tetrazole;UBH-509; D-489; LS 82-556; KPP-300; NC-324; NC-330; KH-218; DPX-N8189;SC-0774; DOWCO-535; DK-8910; V-53482; PP-600; MBH-001; KIH-9201;ET-751;KIH-6127; KIH-2023 and KIH5996.

Controlling harmful plants selectively is of particular interest incrops of useful plants and ornamentals. Even though the compounds (I)already exhibit very good to sufficient selectivity in many crops, it ispossible, in principle, that symptoms of phytotoxicity occur on thecultivated plants in some crops and especially also in the case ofmixtures with other herbicides which are less selective. In thisrespect, combinations of compounds (I) according to the invention whichare of particular interest are those which contain the compounds (I) ortheir combinations with other herbicides or pesticides and safeners. Thesafeners, which are employed in such an amount that they act asantidote, reduce the phytotoxic side effects of herbicides/pesticidesemployed, for example in economically important crops such as cereals(wheat, barley, rye, maize, rice, sorghum and millet), sugar beet, sugarcane, oilseed rape, cotton and soybeans, preferably cereals. Thefollowing groups of compounds are examples of suitable safeners for thecompounds (I) and their combinations with further pesticides:

-   a) compounds of the dichlorophenylpyrazoline-3-carboxylic acid type,    preferably compounds such as ethyl,    1-(2,4-dichlorophenyl)-5-(ethoxycarbonyl)-5-methyl-2-pyrazoline-3-carboxylate    (S1-1) (“Mefenpyr-diethyl”, PM, pp. 594-595) and related compounds    as they are described in WO 91/07874;    dichlorophenylpyrazolecarboxylic acid derivatives, preferably    compounds such as ethyl    1-(2,4-dichlorophenyl)-5-methylpyrazole-3-carboxylate (S1-2), ethyl    1-(2,4-dichlorophenyl)-5-isopropylpyrazole-3-carboxylate (S1-3),    ethyl    1-(2,4-dichlorophenyl)-5-(1,1-dimethylethyl)pyrazole-3-carboxylate    (S1-4), ethyl 1-(2,4-dichlorophenyl)-5-phenylpyrazole-3-carboxylate    (S1-5) and related compounds as they are described in EPA-333 131    and EP-A-269 806;-   c) compounds of the triazolecarboxylic acids type, preferably    compounds such as fenchlorazol (and its ethyl ester), i.e. ethyl    1-(2,4-dichlorophenyl)-5-trichloromethyl-(1H)-1,2,4-triazole-3-carboxylate    (S1-6); and related compounds (see EP-A-174 562 and E-PA-346 620);-   d) compounds of the 5-benzyl- or 5-phenyl-2-isoxazoline-3-carboxylic    acid type or the 5,5-diphenyl-2-isoxazoline-3-carboxylic acid,    preferably compounds such as ethyl    5-(2,4-dichlorobenzyl)-2-isoxazoline-3-carboxylate (S1-7) or ethyl    5-phenyl-2-isoxazoline-3-carboxylate (S1-8) and related compounds as    they are described in WO 91/08202, or ethyl    5,5-diphenyl-2-isoxazolinecarboxylate (S1-9) (“isoxadifen-ethyl”) Or    n-propyl 5,5-diphenyl-2-isoxazolinecarboxylate (S1-10) or ethyl    5-(4-fluorophenyl)-5-phenyl-2-isoxazoline-3-carboxylate (S1-11), as    they are described in German Patent Application (WO-A-95/07897);-   e) compounds of the 8-quinolinoxyacetic acid type (S2), preferably    1-methylhex-1-yl (5-chloro-8-quinolinoxy)acetate (common name    “cloquintocet-mexyl”) (S2-1), (see PM, pp. 1, 95-196)-   1,3-dimethylbut-1-yl (5-chloro-8-quinolinoxy)acetate (S2-2),-   4-allyloxybutyl (5-chloro-8-quinolinoxy)acetate (S2-3),-   1-allyloxyprop-2-yl (5-chloro-8-quinolinoxy)acetate (S2-4),-   ethyl (5-chloro-8-quinolinoxy)acetate (S2-5),-   methyl (5-chloro-8-quinolinoxy)acetate (S2-6),-   allyl (5-chloro-8-quinolinoxy)acetate (S2-7),-   2-(2-propylideneiminooxy)-1-ethyl (5-chloro-8-quinolinoxy)acetate    (S2-8),-   2-oxoprop-1-yl(5-chloro-8-quinolinoxy)acetate (S2-9),    -   and related compounds as are described in EPA-86 750, EP-A-94        349 and EP-A-191 736 or EP-A-0 492 366;-   f) compounds of the (5-chloro-8-quinolinoxy)malonic acid type,    preferably (5-chloro-8-quinolinoxy)malonate, methylethyl    (5-chloro-8-quinolinoxy)malonate and related compounds as are    described in EP-A-0 582 198;-   g) active substances of the phenoxyacetic or phenoxypropionic acid    derivatives type or of the aromatic carboxylic acids type, such as,    for example, 2,4-dichlorophenoxyacetic acids (and its esters)    (2,4-D), 4-chloro-2-methylphenoxypropionic esters (mecoprop), MCPA    or 3,6-dichloro-2-methoxybenzoic acid (and its esters) (dicamba);-   h) active substances of the pyrimidines type which are employed in    rice as soil-acting safeners, such as, for example,    -   “fenclorim” (PM, pp. 386-387)        (=4,6-dichloro-2-phenylpyrimidine), which is also known as        safener for pretilachlor in seeded rice;-   i) active substances of the dichloroacetamides type, which are    frequently employed as pre-emergence safeners (soil-acting    safeners), such as, for example,    -   “dichlormid” (PM, pp. 270-271)        (═N,N-diallyl-2,2-dichloroacetamide),    -   “R-29148” (=3-dichloroacetyl-2,2,5-trimethyl-1,3-oxazolidine, by        Stauffer),    -   “benoxacor” (PM, pp. 74-75)        (=4-dichloroacetyl-3,4-dihydro-3-methyl-2H-1,4-benzoxazine),    -   “PPG-1292”        (═N-allyl-N-[(1,3-dioxolan-2-yl)methyl]dichloroacetamide by PPG        Industries),    -   “DK-24”        (═N-allyl-N-[(allylaminocarbonyl)methyl]dichloroacetamide by        Sagro-Chem),    -   “AD-67” or “MON 4660”        (=3-dichloroacetyl-1-oxa-3-azaspiro[4,5]decane by Nitrokemia and        Monsanto, respectively),    -   “diclonon” or “BAS145138” or “LAB145138”        (=3-dichlbroacetyl-2,5,5-trimethyl-1,3-diazabicyclo[4.3.0]nonane        by BASF) and    -   “furilazol” or “MON 13900” (see PM, 482-483)        (=(RS)-3-dichloroacetyl-5-(2-furyl)-2,2-dimethyloxazolidine);-   j) active substances of the dichloroacetone derivatives type, such    as, for example,    -   “MG 191” (CAS Reg. NO, 96420-72-3)        (=2-dichloromethyl-2-methyl-1,3-dioxolane by Nitrokemia), which        is known as safener for maize;-   k) active substances of the oxyimino compounds type, which are known    as seed, treatment products, such as, for example,    -   “oxabetrinil” (PM, pp. 689)        (=(Z)-1,3-dioxolan-2-ylmethoxyimino(phenyl)-acetonitrile), which        is known as seed-treatment safener for sorghum and millet        against metolachlor damage,    -   “fluxafenim” (PM, pp. 467-468)        (=1-(4-chlorophenyl)-2,2,2-trifluoro-1-ethanone        O-(1,3-dioxolan-2-ylmethyl)oxime, which is known as        seed-dressing safener for sorghum and millet against metolachlor        damage, and    -   “cyometrinil” or “-CGA-43089” (PM, p. 1170)        (=(Z)-cyanomethoxy-imino(phenyl)acetonitrile), which is known as        seed-treatment safener for sorghum and millet against        metolachlor damage;-   l) active substances of the thiazolecarboxylic ester type, which are    known as seed treatment products, such as, for example,    -   “flurazole” (PM, pp. 450451) (=benzyl        2-chloro-4-trifluoromethyl-1,3-thiazole-5-carboxylate), which is        known as seed-treatment safener for sorghum and millet against        alachlor and metolachlor damage;-   m) active substances of the naphthalenedicarboxylic acid derivatives    type, which are known as seed treatment products, such as, for    example,    -   “naphthalic anhydride” (PM, p. 1009-1010)        (=1,8-naphthalenedicarboxylic anhydride), which is known as        seed-treatment safener for maize against thiocarbamate herbicide        damage;-   n) active substances of the chromanacetic acid derivatives type,    such as, for example,    -   “CL 304415” (CAS Reg. No. 31541-57-8)        (=2-(4-carboxychroman-4-yl)acetic acid by American Cyanamid),        which is known as safener for maize against damage by        imidazolinones;-   o) active substances which, in addition to a herbicidal action    against harmful plants, also exhibit a safener action in connection    with crop plants such as rice, such as, for example,    -   “dimepiperate” or “MY-93” (PM, pp. 302-303)        (═S-1-methyl-1-phenylethyl piperidine-1-carbothioate), which is        known as safener for rice against damage by the herbicide        molinate,    -   “daimuron” or “SK 23” (PM, p. 247)        (=1-(1-methyl-1-phenylethyl)-3-p-tolylurea), which is known as        safener for rice against damage by the herbicide imazosulfuron,    -   “cumyluron”=“JC-940”        (=3-(2-chlorophenylmethyl)-1-(1-methyl-1-phenyl-ethyl)urea, see        JP-A-60087254), which is known as safener for rice against        damage by several herbicides,    -   “methoxyphenone” or “NK 049”        (=3,3′-dimethyl-4-methoxybenzophenone), which is known as        safener for rice against damage by several herbicides,    -   “CSB” (=1-bromo-4-(chloromethylsulfonyl)benzene) (CAS Reg. No.        54091-06-4, by Kumiai), which is known as safener in rice        against damage by several herbicides;-   p) N-acylsulfonamides of the formula (S3) and their salts

-   -   as are described in WO-A-97/45016;

-   q) acylsulfamoylbenzamides of the formula (S4), if appropriate also    in salt form,

-   -   as, are described in International Application No.        PCT/EP98/06097; and

-   r) compounds of the formula (S5),

as are described in WO-A 98/13 361,including the stereoisomers and the salts conventionally used inagriculture.

Amongst the safeners, mentioned, those which are of particular interest,are (S1-1) and (S1-9) and (S2-1), in particular (S1-1) and (S1-9).

Some of the safeners are already known as herbicides and thereforesimultaneously also display a protective action in connection with thecrop plants in addition to the herbicidal action in connection withharmful plants.

The weight ratio of herbicide (mixture) to safener generally depends onthe application rate of herbicide and the efficacy of the safener inquestion; it can vary within wide limits, for example in the range offrom 200:1 to 1:200, preferably from 100:1 to 1:100, in particular 20:1to 1:20. The safeners can be formulated with furtherherbicides/pesticides, analogously to the compounds (I) or theirmixtures, and provided and used as readymix or tank mix together withthe herbicides.

For use, the herbicide or herbicide safener formulations, which arepresent in a customary commercial form, are, if appropriate, diluted inthe customary fashion, for example using water in the case of wettablepowders, emulsifiable concentrates, dispersions and water-dispersiblegranules. Preparations in the form, of dusts, soil granules, granulesfor spreading, and sprayable solutions, are usually not diluted furtherwith other inert materials prior to use.

The application rate required of the compounds of the formula (I) varieswith, inter alia, the external conditions such as temperature, humidityand the type of the herbicide used. It can vary within wide limits, forexample between 0.001 and 10.0 kg/ha or more of active substance, but itis preferably between 0.002 and 3 kg/ha, in particular 0.005 and 1kg/ha.

B. Formulation Examples

a) A dust is obtained by mixing 10 parts by weight of a compound offormula (I) and 90 parts by weight of talc as inert material andgrinding the mixture in a hammer mill.

b) wettable powder which is readily dispersible in water is obtained by,mixing 25 parts by weight of a compound of formula (I), 64 parts byweight of kaolin-containing quartz inert material, 10 parts by weight ofpotassium lignosulfonate and 1 part by weight of sodiumoleoylmethyltaurinate as wetter and dispersant and grinding the mixturein a pinned-disk mill.

c) A dispersion concentrate which is readily dispersible in water isobtained by mixing 20 parts by weight of a compound of formula (I) with6 parts by weight of alkylphenol polyglycol ether (®Triton X 207), 3parts by weight of isotridecanol polyglycol ether (8 EO) and 71 parts byweight of paraffinic mineral oil (boiling range for example approx. 255to above 277° C.) and grinding the mixture in a ball mill to a finenessof below 5 microns.

d) An emulsifiable concentrate is obtained from 15 parts by weight of acompound of formula (I), 75 parts by weight of cyclohexanone gas solventand 10 parts by weight of oxethylated nonylphenol as emulsifier.

e) Water-dispersible granules are obtained by mixing

75 parts by weight of a compound of formula (I),10 parts by weight of calcium ligno-sulfonate,5 parts by weight of sodium laurylsulfate,3 parts by Weight of polyvinyl alcohol and7 parts by weight of kaolin,grinding the mixture in a pinned disk mill and granulating the powder ina fluidized bed by spraying on water as granulation liquid.

f) Alternatively, water-dispersible granules are obtained byhomogenizing and precomminuting, on a colloid mill,

25 parts by weight of a compound of (I),5 parts by weight of sodium 2,2′-dinaphthylmethane-6,6′-disulfonate,2 parts by weight of sodium oleoylmethyltaurinate,1 part by weight of polyvinyl alcohol,17 parts by weight of calcium carbonate and50 parts by weight of water,subsequently grinding the mixture on a bead mill and atomizing anddrying the resulting suspension in a spray tower by means of asingle-substance nozzle.

C. Biological Examples Biological Example 1 Pre-Emergence Effect onWeeds

Seeds or rhizome pieces of monocotyledonous and dicotyledonous weedplants were placed in sandy loam in plastic pots and covered with soil.The compounds according to the invention, which were formulated in theform of wettable powders or emulsion concentrates, were then applied, tothe surface of the soil cover as aqueous suspension or emulsion atvarious dosages with an application rate of 600 to 800 l of water per ha(converted).

After the treatment, the pots were placed into a greenhouse and keptunder good growth conditions for the'weeds. The plant or emergence,damage was scored visually after the test plants have emerged after anexperimental time of 3 to 4 weeks by comparison with untreated controls.

Compound numbers 1.1, 1.2, 1.3, 1.7, 1.11, 1.12, 1.15, 1.20, 1.21, 1.24,1.28, 1.31, 1.66, 1.67, 1.68, 1.69, 2.1, 2.2, 2.4, 2.11, 2.25, 2.28,3.1, 3.2, 3.7, 3.11, 3.15, 3.20, 3.24, 4.1, 4.2, 5.1, 5.2, 6.1, 6.2,7.1, 7.2, 7.3, 7.4, 7.11, 7.24, 7.47, 7.48, 7.57, 7.70, 7.72, 7.74,7.75, 7.78, 7.203, 7.228, 7.229, 7.238, 7.239, 7.240, 7.241, 7.242,7.243, 7.244, 7.245, 8.1, 8.2, 8.3, 8.7, 8.11, 8.12, 8.15, 8.21, 8.24,8.25, 8.26, 8.34, 8.35, 8.38, 8.44, 8.48, 8.49, 8.58, 8.61, 8.67, 8.68,8.71, 8.75, 8.79, 8.90, 8.100, 8.113, 8.117, 8.148, 8.152, 8.160, 8.170,8.183, 8.187, 8.195, 8.196, 8.197, 8.201, 8.205, 8.206, 8.209, 8.215,8.219, 8.231, 8.233, 8.234, 8.237, 8.238, 8.239, 8.240, 8.241, 8.242,8.243, 8.244, 8.245, 8.246, 8.247, 8.248, 8.249, 8.250, 8.251, 8.252,8.253, 8.254, 8.255, 8.256, 8.257, 9.36, 9.37, 9.66, 10.1, 10.2, 10.37,10.38, 10.47, 10.57, 10.66, 10.67 and 10.68 according to the inventionshow a very good pre-emergence control of harmful plants such asStellaria media, Lolium multiforum, Amaranthus retroflexus, Sinapisalba, Avena sativa and Setaria viridis when applied at an applicationrate of 1 kg or less of active ingredient per hectare.

Biological Example 2 Post-Emergence Effect on Weeds

Seeds or rhizome pieces of monocotyledonous and dicotyledonous weedswere placed in sandy loam in plastic pots, covered with soil and grownin the greenhouse under good growth conditions. Three weeks aftersowing, the test plants were treated in the three-leaf stage. Variousdosages of the compounds according to the invention, which wereformulated as wettable powders or emulsion concentrates, were sprayed tothe green plant parts at an application rate of 600 to 800 l of waterper ha (converted). After the test plants have been left to stand in thegreenhouse for approx. 3 to 4 weeks under optimal growth conditions, theeffect of the preparations was scored visually by comparison withuntreated controls. Compound numbers 1.1, 1.2, 1.3, 1.7, 1.11, 1.12,1.15, 1.20, 1.21, 1.24, 1.28, 1.31, 1.66, 1.67, 1.68, 1.69, 2.1, 2.2,2.4, 2.11, 2.25, 2.28, 3.1, 3.2, 3.7, 3.11, 3.15, 3.20, 3.24, 4.1, 4.2,5.1, 5.2, 6.1, 6.2, 7.1, 7.2, 7.3, 7.4, 7.11, 7.24, 7.47, 7.48, 7.57,7.70, 7.72, 7.74, 7.75, 7.78, 7.203, 7.228, 7.229, 7.238, 7.239, 7.240,7.241, 7.242, 7.243, 7.244, 7.245, 8.1, 8.2, 8.3, 8.7, 8.11, 8.12, 8.15,8.21, 8.24, 8.25, 8.26, 8.34, 8.35, 8.38, 8.44, 8.48, 8.49, 8.58, 8.61,8.67, 8.68, 8.71, 8.75, 8.79, 8.90, 8.100, 8.113, 8.117, 8.148, 8.152,8.160, 8.170, 8.183, 8.187, 8.195, 8.196, 8.197, 8.201, 8.205, 8.206,6.209, 8.215, 8.219, 8.231, 8.233, 8.237, 8.238, 8.239, 8.240, 8.241,8.242, 8.243, 8.244, 8.245, 8.246, 8.247, 8.248, 8.249, 8.250, 8.251,8.252, 8.253, 8.254, 8.255, 8256, 8.257, 9.36, 9.37, 9.66, 10.1, 10.2,10.37, 10.38, 10.47, 10.57, 10.66, 10.67 and 10.68 according to theinvention show a very good herbicidal post-emergence activity againstharmful plants such as Sinapis alba, Echinochloa crus-galli, Loliummultiflorurn, Stellaria Media, Cyperus iris, Amaranthus retroflexus,Setaria viridis, Avena sativa, Lamium purpureum, Matricaria inodora,Papaver rhoeas, Veronica persica, Viola trocolor, Kochia spp andChenopodium album when applied at an application rate of 2 kg or less ofactive ingredient'per hectare.

Biological Example 3 Weed Control in Plantation Crops

In further field trials plantation crops were grown under conditions ofnatural weed infestation and sprayed with various dosages of thesubstances of formula (I) according to the invention. At various timeintervals after the application it is found by means of visualassessment that the compounds according to the invention leave theplantation crops such as, for example, oil palm, coconut palm,India-rubber tree, citrus, pineapples, cotton, coffee, cocoa and vinesunharmed, even at high rates of active substance. The compounds offormula (I) show an improved degree of selectivity compared to the priorart, and are therefore suitable fix controlling undesired vegetation inplantation crops. Additionally the weeds are very well controlledespecially when applied pre-emergence of the weeds.

1. A compound of the formula (V), or salts thereof,

wherein R⁶ is H, (C₁-C₆)alkyl or (C₁-C₆)alkoxy; R⁷, R⁸, R⁹ and R¹⁰ areeach independently H, (C₁-C₄)alkyl, (C₁-C₃)haloalkyl, halogen,(C₁-C₃)alkoxy, (C₁-C₃)haloalkoxy or CN; A is CH₂, O or a direct bond;and wherein the stereochemical configuration at the marked 1 position is(R) having a stereochemical purity of from 60 to 100% (R), with theexception of compounds of formula (V), or salts thereof, where: (i) A isa direct bond, R⁶, R⁷, R⁸ and R⁹ are each hydrogen, and R¹⁰ is hydrogen,methoxy, n-propoxy or cyano; or A is a direct bond, R⁶, R⁷, R⁸ and R¹⁰are each hydrogen, and R⁹ is fluoro; A is a direct bond, R⁶, R⁹ and R¹⁰are each hydrogen, and R⁷ is methoxy and R⁸ are methoxy; (ii) A is CH₂,and R⁶, R⁷, R⁸ and R¹⁰ are each hydrogen, and R⁹ is hydrogen, methyl,methoxy, isopropoxy, n-propyl or t-butyl; or A is CH₂, and R⁶, R⁷ and R⁹are each hydrogen, and R⁸ is methyl and R¹⁰ is methyl; or A is CH₂, andR⁶, R⁸ and R¹⁰ are each hydrogen, and R⁷ is methyl and R⁹ is methyl; Ais CH₂, and R⁶, R⁷, R⁹ and R¹⁰ are each hydrogen, and R⁸ is methoxy; orA is CH₂, and R⁶, R⁸, R⁹ and R¹⁰ are each hydrogen, and R⁷ is methoxy;or (iii) A is an oxygen atom, and R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each H. 2.The compound of claim 1 which is a compound of the formula (Va) or saltsthereof:

wherein: R⁶ is methyl; R⁷ and R¹⁰ are each independently H or methyl; R⁸is H, methyl, Cl or F; R⁹ is H, methyl, Cl, F or Br; and A is a directbond, CH₂ or O and the stereochemical configuration at the marked 1position is (R) having a stereochemical purity of from 60 to 100% (R),and the stereochemical configuration at the marked 2 position is (S)having a stereochemical purity of from 60 to 100% (S).
 3. The compoundof claim 1 which is a compound of the formula (Vb) or salts thereof:

wherein: R⁶ is methyl; R⁷ and R¹⁰ are each independently H or methyl; R⁸is H, methyl, Cl or F; R⁹ is H, methyl, Cl, F or Br; and A is a directbond, CH₂ or O and the stereochemical configuration at the marked 1position is (R) having a stereochemical purity of from 60 to 100% (R),and the stereochemical configuration at the marked 2 position is (R)having a stereochemical purity of from 60 to 100% (R).
 4. A compound offormula (XIII) or a salt thereof,

in which R⁶ is H, (C₁-C₆)alkyl or (C₁-C₆)alkoxy; and R⁷, R⁸, R⁹ and R¹⁰are each independently H, (C₁-C₄)alkyl, (C₁-C₃)haloalkyl, halogen,(C₁-C₃)alkoxy, (C₁-C₃)haloalkoxy or CN; R¹¹ is (C₁-C₆)alkanoyl which isunsubstituted or substituted by one or more radicals selected from thegroup consisting of halogen, (C₁-C₄)alkoxy and (C₁-C₄)alkylthio; A isCH₂, O or a direct bond; and wherein the stereochemical configuration atthe marked 1 position is (R) having a stereochemical purity of from 60to 100% (R), with the exception of compounds of formula (XIII), or saltsthereof, where: (i) A is a direct bond, R⁶, R⁷, R⁸, R⁹ and R¹⁰ are eachhydrogen, and R¹¹ is formyl, acetyl, propionyl, n-butanoyl, n-hexanoyl,trifluoroacetyl or bromacetyl; or A is a direct bond, R⁶ is methyl; R⁷,R⁸, R⁹ and R¹⁰ are each hydrogen, and R¹¹ is acetyl, or A is a directbond, R⁶; R⁷, R⁹ and R¹⁰ are each hydrogen, R⁸ is fluoro, and R¹¹ isacetyl, or A is a direct bond, R⁶; R⁷, R⁸ and R¹⁰ are each hydrogen, R⁹is fluoro, and R¹¹ is acetyl, or A is a direct bond, R⁶; R⁹ and R¹⁰ areeach hydrogen, R⁷ is methoxy, and R⁸ is methoxy, or (ii) A is CH₂, andR⁶, R⁷, R⁸, R⁹ and R¹⁰ are each hydrogen, and R¹¹ is acetyl,trifluoroacetyl, chloroacetyl or butanoyl; or A is CH₂, and R⁶, R⁷ andR⁹ are each hydrogen, and R⁸ is methyl and R¹⁰ is methyl; and R¹¹ isacetyl, or A is CH₂, and R⁶, R⁷, R⁹ and R¹⁰ are each hydrogen, and R⁸ ismethoxy, and R¹¹ is acetyl, or A is CH₂, and R⁶ is methyl, R⁷, R⁸, R⁹and R¹⁰ are each hydrogen, and R¹¹ is acetyl, or A is CH₂, and R⁶, R⁸,R⁹, and R¹⁰ are each hydrogen, R⁷ is methoxy, and R¹¹ is bromoacetyl orchloropropionyl; or A is CH₂, and R⁶, R⁸ and R¹⁰ are each hydrogen, andR⁷ is methyl and R⁹ is methyl; and R¹¹ is acetyl, or A is CH₂, and R⁷,R⁸, R⁹ and R¹⁰ are each hydrogen, R⁶ is methyl, and R¹¹ is acetyl; or(iii) A is an oxygen atom, and R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each H, andR¹¹ is acetyl.
 5. The compound of claim 4 which is a compound of formula(XIII) or a salt thereof,

wherein: R⁶ is methyl; R⁷ and R¹⁰ are each independently H or methyl; R⁸is H, methyl, Cl or F; R⁹ is H, methyl, Cl, F or Br; and R¹¹ is(C₁-C₆)alkanoyl which is unsubstituted or substituted by one or moreradicals selected from the group consisting of halogen, (C₁-C₄)alkoxyand (C₁-C₄)alkylthio; A is a direct bond, CH₂ or O and thestereochemical configuration at the marked 1 position is (R) having astereochemical purity of from 60 to 100% (R), and the stereochemicalconfiguration at the marked 2 position is (S) having a stereochemicalpurity of from 60 to 100% (S).
 6. A compound of formula (III) or a saltthereof,

wherein R⁴ and R⁵ are each independently H, (C₁-C₄)alkyl,(C₁-C₄)haloalkyl, (C₃-C₄)alkenyl, (C₃-C₄)haloalkenyl, (C₃-C₄)alkynyl,(C₃-C₄)haloalkynyl or an acyl radical; R⁶ is H, (C₁-C₆)alkyl or(C₁-C₆)alkoxy; R⁷, R⁸, R⁹ and R¹⁰ are each independently H,(C₁-C₄)alkyl, (C₁-C₃)haloalkyl, halogen, (C₁-C₃)alkoxy,(C₁-C₃)haloalkoxy or CN; A is CH₂, O or a direct bond; and thestereochemical configuration at the marked 1 position is (R) having astereochemical purity of from 60 to 100% (R).
 7. A compound of formula(III) or a salt thereof as claimed in claim 16, wherein R⁶ is(C₁-C₆)alkyl, and the stereochemical configuration at the marked 2position is (S) having a stereochemical purity of from 60 to 100% (S).